Co-reporter:Dengfeng Hu, Huan Li, Bailiang Wang, Zi Ye, Wenxi Lei, Fan Jia, Qiao Jin, Ke-Feng Ren, and Jian Ji
ACS Nano September 26, 2017 Volume 11(Issue 9) pp:9330-9330
Publication Date(Web):August 14, 2017
DOI:10.1021/acsnano.7b04731
Biofilms that contribute to the persistent bacterial infections pose serious threats to global public health, mainly due to their resistance to antibiotics penetration and escaping innate immune attacks by phagocytes. Here, we report a kind of surface-adaptive gold nanoparticles (AuNPs) exhibiting (1) a self-adaptive target to the acidic microenvironment of biofilm, (2) an enhanced photothermal ablation of methicillin-resistant Staphylococcus aureus (MRSA) biofilm under near-infrared (NIR) light irradiation, and (3) no damage to the healthy tissues around the biofilm. Originally, AuNPs were readily prepared by surface modification with pH-responsive mixed charged zwitterionic self-assembled monolayers consisting of weak electrolytic 11-mercaptoundecanoic acid (HS-C10-COOH) and strong electrolytic (10-mercaptodecyl)trimethylammonium bromide (HS-C10-N4). The mixed charged zwitterion-modified AuNPs showed fast pH-responsive transition from negative charge to positive charge, which enabled the AuNPs to disperse well in healthy tissues (pH ∼7.4), while quickly presenting strong adherence to negatively charged bacteria surfaces in MRSA biofilm (pH ∼5.5). Simultaneous AuNP aggregation within the MRSA biofilm enhanced the photothermal ablation of MRSA biofilm under NIR light irradiation. The surrounding healthy tissues showed no damage because the dispersed AuNPs had no photothermal effect under NIR light. In view of the above advantages as well as the straightforward preparation, AuNPs developed in this work may find potential applications as a useful antibacterial agent in the areas of healthcare.Keywords: biofilm; gold nanoparticles; mixed charged zwitterion; pH-responsive; photothermal therapy;
Co-reporter:Jina Wu, Haijie Han, Qiao Jin, Zuhong Li, Huan Li, and Jian Ji
ACS Applied Materials & Interfaces May 3, 2017 Volume 9(Issue 17) pp:14596-14596
Publication Date(Web):April 11, 2017
DOI:10.1021/acsami.6b15853
5-Aminolevulinic acid (ALA), the precursor of photosensitizer protoporphyrin IX (PpIX), is a U.S. FDA-approved photodynamic therapeutic agent. However, realizing efficient delivery of ALA is still a big challenge as it is hydrophilic and cannot be recognized and selectively accumulated in tumor cells. In this study, matrix metalloproteinase-2 (MMP-2) and pH dual-sensitive ALA prodrug nanocarriers were constructed as a programmed delivery strategy for the targeted delivery of ALA. The nanocarriers were prepared by the co-modification of gold nanoparticles (AuNPs) with hydrazone-linked ALA and MMP-2-activatable cell-penetrating peptides (CPPs). Cationic CPP RRRRRRRR (R8) was shielded by zwitterionic stealth peptide EKEKEKEKEKEKEKEKEKEK (EK10) via MMP-2 substrate peptide PLGLAG. The zwitterionic stealth peptide EK10 is designed to endow ALA prodrug nanocarriers with strong antifouling ability and prolonged circulation time. Upon arriving at the tumor tissue, the shielded cationic CPP R8 can be activated by tumor-microenvironment-overexpressed MMP-2, which enabled enhanced cellular uptake of ALA. The results of drug loading and release, cellular uptake, PpIX generation and accumulation, photodynamic cytotoxicity, and photodynamic tumor inhibition demonstrated that such tumor-microenvironment-sensitive ALA prodrug nanocarriers could be considered as potential candidates for targeted photodynamic cancer therapy.Keywords: 5-aminolevulinic acid; enzyme; photodynamic cancer therapy; prodrug nanocarriers; programmed targeting;
Co-reporter:Mi Hu;Li-mei Wang;He Zhang;Hao Chang;Huan Li;Wen-xi Lei;Bo-chao Li;Ke-feng Ren
ACS Applied Materials & Interfaces June 15, 2016 Volume 8(Issue 23) pp:14357-14366
Publication Date(Web):2017-2-22
DOI:10.1021/acsami.6b01870
Endothelialization on the vascular implants is of great importance for prevention of undesired postimplantation symptoms. However, endothelial dysfunction of regenerated endothelial cell (EC) monolayer has been frequently observed, leading to severe complications, such as neointimal hyperplasia, late thrombosis, and neoatherosclerosis. It has significantly impeded long-term success of the therapy. So far, very little attention has been paid on endothelial function of EC monolayer. Bioinspired by the microenvironment of the endothelium in a blood vessel, this study described a soft polyelectrolyte multilayer film (PEM) through layer-by-layer assembly of poly(l-lysine) (PLL) and hyaluronan (HA). The (PLL/HA) PEM was chemically cross-linked and further incorporated with vascular endothelial growth factor. It demonstrated that this approach could promote EC adhesion and proliferation, further inducing formation of EC monolayer. Further, improved endothelial function of the EC monolayer was achieved as shown with the tighter integrity, higher production of nitric oxide, and expression level of endothelial function related genes, compared to EC monolayers on traditional substrates with high stiffness (e.g., glass, tissue culture polystyrene, and stainless steel). Our findings highlighted the influence of substrate stiffness on endothelial function of EC monolayer, giving a new strategy in the surface design of vascular implants.Keywords: endothelial function; endothelialization; polyelectrolyte multilayer film; stiffness; vascular endothelial growth factor;
Co-reporter:Tingting Chen, Haijie Han, Fan Jia, Qiao Jin, and Jian Ji
The Journal of Physical Chemistry C June 1, 2017 Volume 121(Issue 21) pp:11144-11144
Publication Date(Web):May 11, 2017
DOI:10.1021/acs.jpcc.7b02759
A suitable deformation rate is crucial for shape memory polymers (SMPs) in real word applications. Yet on-demand modulation in shape recovery kinetics and its spatial heterogeneous control still need to be explored systematically. Herein, a near-infrared (NIR) light controlling strategy was demonstrated for in situ modulation in both shape recovery rate and its spatial heterogeneity. Polyvinyl alcohol and chitosan, two typical SMPs, were chosen to elaborate the strategy, due to their heat-responsive shape memory effect (SME) and chemoresponsive SME, respectively. Reduced graphene oxide was incorporated in the SMPs to endow them with NIR light controllability. Through light intensity adjustment, the shape recovery rate could be altered by nearly an order of magnitude without any modification of material composition. Similar shape transition kinetics at different ambient temperatures could be achieved. More impressively, spatially modulated recovery kinetics was successfully conducted to avoid undesired self-collisions or self-interferences in complex shape shifting processes and thus prevent possible shape transition failure. As the regulatory information was not encoded in the SMPs, deformation rate and its spatial differentiation could be adjusted flexibly after material preparation, allowing the adaptability of the shape shifting process under conditions with individual differences.
Co-reporter:Xia-chao Chen, Ke-feng Ren, Jing Wang, Wen-xi Lei, and Jian Ji
ACS Applied Materials & Interfaces 2017 Volume 9(Issue 2) pp:
Publication Date(Web):December 22, 2016
DOI:10.1021/acsami.6b14081
Introducing a lubricant layer onto surfaces has emerged as a novel strategy to address a wide range of interface-related challenges. Recent studies of lubricant-infused surfaces have extended beyond repelling liquids to manipulating the mobility of fluids. In this study, we report a design of slippery surfaces based on infusing lubricant onto a polyelectrolyte multilayer film whose surface microstructures can be erased rapidly under mild condition. Unlike other lubricant-infused surfaces, the liquid movements (e.g., moving resistance and direction) on such surfaces can be manipulated via programming the surface microstructures beforehand. The work reported here offers a versatile design concept of lubricant-infused surfaces and may turn on new applications of this emerging class of bioinspired materials.Keywords: erasable microstructures; guided sliding; liquid movement; lubricant-infused surfaces; polyelectrolyte multilayer films;
Co-reporter:Haijie Han, Daniel ValdepérezQiao Jin, Bin Yang, Zuhong Li, Yulian Wu, Beatriz Pelaz, Wolfgang J. Parak, Jian Ji
ACS Nano 2017 Volume 11(Issue 2) pp:
Publication Date(Web):January 10, 2017
DOI:10.1021/acsnano.6b05541
Dual enzymatic reactions were introduced to fabricate programmed gemcitabine (GEM) nanovectors for targeted pancreatic cancer therapy. Dual-enzyme-sensitive GEM nanovectors were prepared by conjugation of matrix metalloproteinase-9 (MMP-9) detachable poly(ethylene glycol) (PEG), cathepsin B-cleavable GEM, and targeting ligand CycloRGD to CdSe/ZnS quantum dots (QDs). The GEM nanovectors decorated with a PEG corona could avoid nonspecific interactions and exhibit prolonged blood circulation time. After GEM nanovectors were accumulated in tumor tissue by the enhanced permeability and retention (EPR) effect, the PEG corona can be removed by overexpressed MMP-9 in tumor tissue and RGD would be exposed, which was capable of facilitating cellular internalization. Once internalized into pancreatic cancer cells, the elevated lysosomal cathepsin B could further promote the release of GEM. By employing dual enzymatic reactions, the GEM nanovectors could achieve prolonged circulation time while maintaining enhanced cellular internalization and effective drug release. The proposed mechanism of the dual enzymatic reaction-assisted GEM delivery system was fully investigated both in vitro and in vivo. Meanwhile, compared to free GEM, the deamination of GEM nanovectors into inactive 2′,2′-difluorodeoxyuridine (dFdU) could be greatly suppressed, while the concentration of the activated form of GEM (gemcitabine triphosphate, dFdCTP) was significantly increased in tumor tissue, thus exhibiting superior tumor inhibition activity with minimal side effects.Keywords: enzyme sensitive; gemcitabine; pancreatic cancer therapy; programmed targeting; tumor microenvironment;
Co-reporter:Hao Chang, He Zhang, Mi Hu, Jia-yan Chen, Bo-chao Li, Ke-feng Ren, M.Cristina L. Martins, Mário A. Barbosa, Jian Ji
Colloids and Surfaces B: Biointerfaces 2017 Volume 149() pp:379-387
Publication Date(Web):1 January 2017
DOI:10.1016/j.colsurfb.2016.11.012
•VEGF-bound (PLL/HA) films with controlled stiffness are constructed.•Comparable EC monolayers are formed on both soft and stiff films.•Endothelial function displays a negatively correlation with substrate stiffness.Endothelialization has proved to be critical for maintaining long-term success of implantable vascular devices. The formation of monolayer of endothelial cells (ECs) on the implant surfaces is one of the most important factors for the endothelialization. However, endothelial function of regenerated EC monolayer, which plays a much more important role in preventing the complications of post-implantation, has not received enough attention. Here, a vascular endothelial growth factor (VEGF)-incorporated poly(l-lysine)/hyaluronan (PLL/HA) polyelectrolyte multilayer film was fabricated. Through varying the crosslinking degree, stiffness of the film was manipulated, offering either soft or stiff film. We demonstrated that ECs were able to adhere and proliferate on both soft and stiff films, subsequently forming an integrated EC monolayer. Furthermore, endothelial functions were evaluated by characterizing EC monolayer integrity, expression of genes correlated with the endothelial functions, and nitric oxide production. It demonstrated that EC monolayer on the soft film displayed higher endothelial function compared to that on the stiff film. Our study highlights the influence of substrate stiffness on endothelial function, which offers a new criterion for surface design of vascular implants.
Co-reporter:Haijie Han;Wenzhuo Teng;Tingting Chen;Jue Zhao;Qiao Jin;Zhihui Qin
Chemical Communications 2017 vol. 53(Issue 66) pp:9214-9217
Publication Date(Web):2017/08/15
DOI:10.1039/C7CC04872F
A targeted cathepsin B-activatable gemcitabine prodrug with caspase-3 specific light-up tetraphenylene (TPE) as an apoptotic probe based on aggregation-induced emission (AIE) properties was designed for in situ self-therapeutic monitoring of pancreatic cancer cells.
Co-reporter:Haijie Han, Haibo Wang, Yangjun Chen, Zuhong Li, Yin Wang, Qiao Jin and Jian Ji
Nanoscale 2016 vol. 8(Issue 1) pp:283-291
Publication Date(Web):09 Nov 2015
DOI:10.1039/C5NR06734K
A biodegradable and reduction-cleavable gemcitabine (GEM) polymeric prodrug with in vivo near-infrared (NIR) imaging ability was reported. This theranostic GEM prodrug PEG-b-[PLA-co-PMAC-graft-(IR820-co-GEM)] was synthesized by ring-opening polymerization and “click” reaction. The as-prepared reduction-sensitive prodrug could self-assemble into prodrug micelles in aqueous solution confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). In vitro drug release studies showed that these prodrug micelles were able to release GEM in an intracellular-mimicking reductive environment. These prodrug micelles could be effectively internalized by BxPC-3 pancreatic cancer cells, which were observed by confocal laser scanning microscopy (CLSM). Meanwhile, a methyl thiazolyl tetrazolium (MTT) assay demonstrated that this prodrug exhibited high cytotoxicity against BxPC-3 cells. The in vivo whole-animal near-infrared (NIR) imaging results showed that these prodrug micelles could be effectively accumulated in tumor tissue and had a longer blood circulation time than IR820-COOH. The endogenous reduction-sensitive gemcitabine prodrug micelles with the in vivo NIR imaging ability might have great potential in image-guided pancreatic cancer therapy.
Co-reporter:Hongxin Tong, Yin Wang, Huan Li, Qiao Jin and Jian Ji
Chemical Communications 2016 vol. 52(Issue 20) pp:3966-3969
Publication Date(Web):08 Feb 2016
DOI:10.1039/C6CC00450D
Novel 5-aminolevulinic acid (ALA) pseudopolyrotaxane prodrug micelles with dual pH-responsive properties were prepared by the host–guest interaction of α-cyclodextrin (α-CD) and poly(ethylene glycol) (PEG). The micelles exhibited pH dependent cellular uptake and pH-sensitive ALA release, enabling enhanced photodynamic therapy.
Co-reporter:Yin Wang, Huan Li, Qiao Jin and Jian Ji
Chemical Communications 2016 vol. 52(Issue 3) pp:582-585
Publication Date(Web):30 Oct 2015
DOI:10.1039/C5CC07195J
A simple method to achieve host–guest assembly of gold nanoparticles triggered by intracellular glutathione was demonstrated. The increased size of nanoparticles not only enhanced their retention time within cancer cells, but also induced apoptosis. This strategy may open an avenue for the development of smart nanocarriers for intracellular diagnosis and therapy.
Co-reporter:Yangjun Chen, Zuhong Li, Haibo Wang, Yin Wang, Haijie Han, Qiao Jin, and Jian Ji
ACS Applied Materials & Interfaces 2016 Volume 8(Issue 11) pp:6852
Publication Date(Web):February 26, 2016
DOI:10.1021/acsami.6b00251
IR-780 iodide, a near-infrared (near-IR) fluorescent dye, can be utilized as an effective theranostic agent for both imaging and photothermal therapy. However, its lipophilicity limits its further biomedical applications. Herein, we synthesized a phospholipid mimicking amphiphilic homopolymer poly(12-(methacryloyloxy)dodecyl phosphorylcholine) (PMDPC) via reversible addition–fragmentation chain transfer (RAFT) polymerization. The amphiphilic homopolymer PMDPC can be self-assembled into micelles and used for the encapsulation of IR-780. The IR-780 loaded micelles (PMDPC-IR-780) exhibited low cytotoxicity in the dark, whereas remarkable photothermal cytotoxicity to pancreatic cancer cells (BxPC-3) was observed upon near-IR laser irradiation. We further investigated in vivo biodistribution of PMDPC-IR-780 micelles. Higher accumulation of PMDPC-IR-780 than that of free IR-780 in tumor tissue was verified, which might be ascribed to the enhanced permeability and retention (EPR) effect and long circulation time benefiting from the zwitterionic phosphorylcholine surface. Therefore, the IR-780 loaded phospholipid mimicking homopolymeric micelles could have great potential for cancer theranostics.Keywords: homopolymeric micelle; IR-780 dye; near-infrared (near-IR) imaging; pancreatic cancer; photothermal therapy; zwitterion
Co-reporter:Xia-chao Chen, Ke-feng Ren, Wen-xi Lei, Jia-hui Zhang, M. Cristina L. Martins, Mário A. Barbosa, and Jian Ji
ACS Applied Materials & Interfaces 2016 Volume 8(Issue 7) pp:4309
Publication Date(Web):February 4, 2016
DOI:10.1021/acsami.5b11602
Optimized ratio in the codelivery of therapeutics is of crucial importance to promote the synergism rather than the antagonistic effects. In this study, a self-healing spongy coating was described to facilitate the surface-mediated delivery of drug “cocktails” proportionally. The formation of spongy structures within the coating was achieved by acidic treatment and freeze-drying. Various drug combinations can be readily integrated through wicking method and subsequent micropore self-healing. The ratio of drug loading can be precisely regulated by the composition of loading solution and the embedded drugs were released in proportion according to the initial ratio of drug combination.Keywords: drug combination; polyelectrolyte multilayers; proportional codelivery; self-healing; spongy coating
Co-reporter:Yangjun Chen, Haijie Han, Hongxin Tong, Tingting Chen, Haibo Wang, Jian Ji, and Qiao Jin
ACS Applied Materials & Interfaces 2016 Volume 8(Issue 33) pp:21185
Publication Date(Web):August 2, 2016
DOI:10.1021/acsami.6b06071
Polymeric micelles have emerged as a promising nanoplatform for cancer theranostics. Herein, we developed doxorubicin (DOX) encapsulated pH-responsive polymeric micelles for combined aggregation induced emission (AIE) imaging and chemotherapy. The novel zwitterionic copolymer poly(2-methacryloyloxyethylphosphorylcholine-co-2-(4-formylphenoxy)ethyl methacrylate) (poly(MPC-co-FPEMA)) was synthesized via RAFT polymerization and further converted to PMPC-hyd-TPE after conjugation of tetraphenylethene (TPE, a typical AIE chromophore) via acid-cleavable hydrazone bonds. The AIE activatable copolymer PMPC-hyd-TPE could self-assemble into spherical PC-hyd-TPE micelles, and DOX could be loaded through hydrophobic interactions. The zwitterionic micelles exhibited excellent physiological stability and low protein adsorption due to the stealthy phosphorylcholine (PC) shell. In addition, the cleavage of hydrophobic TPE molecules under acidic conditions could induce swelling of micelles, which was verified by size changes with time at pH 5.0. The in vitro DOX release profile also exhibited accelerated release rate with pH value decreasing from 7.4 to 5.0. Fluorescent microscopy and flow cytometry studies further demonstrated fast internalization and accumulation of drug loaded PC-hyd-TPE-DOX micelles in HepG2 cells, resulting in considerable time/dose-dependent cytotoxicity. Meanwhile, high-quality AIE imaging of PC-hyd-TPE micelles was confirmed in HepG2 cells. Notably, ex vivo imaging study exhibited efficient accumulation and drug release of PC-hyd-TPE-DOX micelles in the tumor tissue. Consequently, the multifunctional micelles with combined nonfouling surface, AIE active imaging, and pH-responsive drug delivery showed great potential as novel nanoplatforms for a new generation of cancer theranostics.Keywords: aggregation induced emission; bioimaging; drug delivery; pH-responsive; theranostics; zwitterionic polymers
Co-reporter:Wenshu Zheng, Huan Li, Wenwen Chen, Jian Ji, and Xingyu Jiang
Analytical Chemistry 2016 Volume 88(Issue 7) pp:4140
Publication Date(Web):March 9, 2016
DOI:10.1021/acs.analchem.6b00501
This report describes a colorimetric assay for trivalent metal cations (M3+) using gold nanoparticles (AuNPs)-modified with oppositely charged thiols that can form intermolecular zwitterionic surfaces. Zwitterionic AuNPs (Zw-AuNPs) are stable in high-salt solutions and well-dispersed in a wide range of pH values. M3+ including Fe3+, Al3+, and Cr3+ can effectively trigger the aggregation of Zw-AuNPs by interfering with their surface potential, and aggregated AuNPs can be regenerated and recycled by removing M3+. In our approach, the output signal can be observed by the naked eye within a micromolar (μM) concentration range. Uniquely, our assay is capable of discriminating Fe3+ from Fe2+, which is challenging using traditional approaches. More importantly, Zw-AuNPs can be stored stably at room temperature for a long period (3 months) with constant detection performance. Both the cost-effectiveness and the long shelf life make Zw-AuNPs ideal for detecting M3+ in resource-poor and remote areas.
Co-reporter:Yangjun Chen, Yin Wang, Haibo Wang, Fan Jia, Tongjiang Cai, Jian Ji, Qiao Jin
Polymer 2016 Volume 97() pp:449-455
Publication Date(Web):5 August 2016
DOI:10.1016/j.polymer.2016.05.051
•The prodrug nanoparticles are formed based on host-guest interactions.•The prodrug nanoparticles possess zwitterionic phosphorylcholine surface.•The prodrug nanoparticles exhibit pH-responsive drug release profile.•The prodrug nanoparticles can efficiently delivery DOX into cancer cells.A novel zwitterionic pendant copolymer poly(2-(methacryloyloxy)ethyl phosphorylcholine)-co-poly(2-(methacryloyloxy)ethyl adamantane-1-carboxylate) (poly(MPC-co-Ada)) is synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. The pendant adamantane guest molecules and doxorubicin (DOX) decorated β-cyclodextrins (DOX-hyd-CD) can form inclusion complexation through host-guest interactions. The resultant supramolecular polymers can self-assemble into polymeric prodrug nanoparticles in the size range of 25–60 nm, with the zwitterionic phosphorylcholine grafts acting as hydrophilic shell. In vitro drug release results indicates that the release of DOX at pH 5.0 is faster than that at pH 7.4, since DOX is conjugated to β-CD with pH-responsive hydrazone bond. Efficient cellular internalization is observed by flow cytometry and fluorescence microscopy, resulting in the inhibitation of cancer cell proliferation. Importantly, taking advantage of the host-guest interaction, such kind of zwitterionic pendant polymer can be further developed as promising platforms for multifunctional cancer theranostics.
Co-reporter:Haijie Han, Shimiao Zhang, Yin Wang, Tingting Chen, Qiao Jin, Yangjun Chen, Zuhong Li, Jian Ji
Polymer 2016 Volume 82() pp:255-261
Publication Date(Web):15 January 2016
DOI:10.1016/j.polymer.2015.11.022
•Theranostic nanoparticles were easily obtained by miniemulsion polymerization.•The as-prepared nanoparticles showed good monodispersity and significant stability.•The nanoparticles possessed better photothermal cytotoxicity than free IR-820.•The nanoparticles showed better diagnosis effects than free IR-780.Miniemulsion reversible addition-fragmentation chain transfer (RAFT) polymerization was used to synthesize biomimetic poly (2-methacryloyloxyethyl phosphorylcholine)-b-Poly (n-butyl methacrylate) (PMPC-b-PBMA) nanoparticles which were used as nanocarriers to encapsulate theranostic IR-780 molecules. IR-780 endowed the PMPC-b-PBMA nanoparticles with dual functions including tumor near-infrared (NIR) imaging and photothermal therapy (PTT). The IR-780 encapsulated PMPC-b-PBMA (PMPC-b-PBMA/IR-780) nanoparticles showed good monodispersity and significant stability. The photothermal effects and photothermal cytotoxicity of the PMPC-b-PBMA/IR-780 nanoparticles were studied in vitro. High accumulation of the PMPC-b-PBMA/IR-780 nanoparticles in tumor tissue was verified by whole-animal NIR imaging. The resulted IR-780 encapsulated biomimetic nanoparticles can be an alternative safe theranostic agent for imaging-guided cancer treatment.
Co-reporter:Bo-chao Li, Hao Chang, Ke-feng Ren, Jian Ji
Colloids and Surfaces B: Biointerfaces 2016 Volume 147() pp:172-179
Publication Date(Web):1 November 2016
DOI:10.1016/j.colsurfb.2016.07.063
•A substrate-mediated delivery of hepatocyte growth factor (HGF) plasmid DNA.•HGF-pDNA nanoparticles were steadily immobilized onto polydopamine (PDA) coating.•Both adhered endothelial and smooth muscle cells were directly transfected.•The competitiveness of endothelial cells was enhanced because of improved HGF expression.Substrate-mediated delivery of functional plasmid DNA (pDNA) has been proven to be a promising strategy to promote competitiveness of endothelial cells (ECs) over smooth muscle cells (SMCs), which is beneficial to inducing fast endothelialization of implanted vascular devices. Thus, it is of great importance to develop universal approaches with simplicity and easiness to immobilize DNA complex nanoparticles on substrates. In this study, the bioinspired polydopamine (PDA) coating was employed in immobilization of DNA complex nanoparticles, which were composed of protamine (PrS) and plasmid DNA encoding with hepatocyte growth factor (HGF-pDNA) gene. We demonstrated that the DNA complex nanoparticles can be successfully immobilized onto the PDA surface. Consequently, the HGF expression of both ECs and SMCs were significantly improved when they cultured on the DNA complex nanoparticles-immobilized substrates. Furthermore, EC proliferation was specifically promoted due to bioactivity of HGF, leading to an enhancement of EC competitiveness over SMCs. Our findings demonstrated the substrate-mediated functional gene nanoparticle delivery through PDA coating as a simple and efficient approach. It may hold great potential in the field of interventional cardiovascular implants.A substrate-mediated delivery of gene complex nanoparticles containing hepatocyte growth factor plasmid DNA for enhancing endothelial cell competitiveness is reported.
Co-reporter:Hao Chang, Xi-qiu Liu, Mi Hu, He Zhang, Bo-chao Li, Ke-feng Ren, Thomas Boudou, Corinne Albiges-Rizo, Catherine Picart, and Jian Ji
Biomacromolecules 2016 Volume 17(Issue 9) pp:2767
Publication Date(Web):July 18, 2016
DOI:10.1021/acs.biomac.6b00318
Endothelial cells (ECs) play a crucial role in regulating various physiological and pathological processes. The behavior of ECs is modulated by physical (e.g., substrate stiffness) and biochemical cues (e.g., growth factors). However, the synergistic influence of these cues on EC behavior has rarely been investigated. In this study, we constructed poly(l-lysine)/hyaluronan (PLL/HA) multilayer films with different stiffness and exposed ECs to these substrates with and without hepatocyte growth factor (HGF)-supplemented culture medium. We demonstrated that EC adhesion, migration, and proliferation were positively correlated with substrate stiffness and that these behaviors were further promoted by HGF. Interestingly, ECs on the lower stiffness substrates showed stronger responses to HGF in terms of migration and proliferation, suggesting that HGF can profoundly influence stiffness-dependent EC behavior correlated with EC growth. After the formation of an EC monolayer, EC behaviors correlated with endothelial function were evaluated by characterizing monolayer integrity, nitric oxide production, and gene expression of endothelial nitric oxide synthase. For the first time, we demonstrated that endothelial function displayed a negative correlation with substrate stiffness. Although HGF improved endothelial function, HGF was not able to change the stiffness-dependent manner of endothelial functions. Taken together, this study provides insights into the synergetic influence of physical and biochemical cues on EC behavior and offers great potential in the development of optimized biomaterials for EC-based regenerative medicine.
Co-reporter:Lin Wang;Haoke Zhang;Anjun Qin;Qiao Jin;Ben Zhong Tang
Science China Chemistry 2016 Volume 59( Issue 12) pp:1609-1615
Publication Date(Web):2016 December
DOI:10.1007/s11426-016-0246-9
Theranostic hyaluronic acid (HA) prodrug micelles with pH-responsive drug release and aggregation-induced emission (AIE) properties were prepared by chemical graft of biomimetic phosphorylcholine (PC), anticancer drug doxorubicin (DOX) and AIE fluorogen tetraphenylene (TPE) to the HA backbone. DOX was conjugated to the HA backbone by a hydrazone bond which can be hydrolyzed under acidic environment and result in pH-triggered smart release of DOX. The TPE units with typical AIE characteristics were applied for real time drug tracking in cancer cells. The HA-based prodrugs could self-assemble into micelles in aqueous solution as confirmed by the dynamic light scattering (DLS) and transmission electron microscopy (TEM). The intracellular distribution of HA prodrug micelles could be clearly observed by fluorescence microscopy based on the strong fluorescence of TPE. Moreover, after treated with the micelles, stronger fluorescence of TPE in CD44 overexpressed MDA-MB-231 cancer cells was observed, compared to the CD44 negative cell line, NIH3T3 cells, suggesting efficient cell uptake of HA prodrug micelles by receptor-mediated endocytosis. The cell viability results indicated that the prodrug micelles could inhibit the proliferation of the cancer cells effectively. Such pH-triggered theranostic drug delivery system with AIE features can provide a new platform for targeted and image-guided cancer therapy.
Co-reporter:Xia-Chao Chen;Ke-Feng Ren;Jia-Hui Zhang;Dan-Dan Li;Emily Zhao;Zhong Jonathon Zhao;Zhi-Kang Xu
Advanced Functional Materials 2015 Volume 25( Issue 48) pp:7470-7477
Publication Date(Web):
DOI:10.1002/adfm.201503258
Layer-by-layer (LbL) self-assemblies have inherent potential as dynamic coatings because of the sensitivity of their building blocks to external stimuli. Here, humidity serves as a feasible trigger to activate the self-healing of a microporous polyethylenimine/poly(acrylic acid) multilayer film. Microporous structures within the polyelectrolyte multilayer (PEM) film are created by acid treatment, followed by freeze-drying to remove water. The self-healing of these micropores can be triggered at 100% relative humidity, under which condition the mobility of the polyelectrolytes is activated. Based on this, a facile and versatile method is suggested for directly integrating hydrophobic drugs into PEM films for surface-mediated drug delivery. The high porosity of microporous film enables the highest loading (≈303.5 μg cm−2 for a 15-bilayered film) of triclosan to be a one-shot process via wicking action and subsequent solvent removal, thus dramatically streamlining the processes and reducing complexities compared to the existing LbL strategies. The self-healing of a drug-loaded microporous PEM film significantly reduces the diffusion coefficient of triclosan, which is favorable for the long-term sustained release of the drug. The dynamic properties of this polymeric coating provide great potential for its use as a delivery platform for hydrophobic drugs in a wide variety of biomedical applications.
Co-reporter:Haibo Wang, Xiangsheng Liu, Yin Wang, Yangjun Chen, Qiao Jin and Jian Ji
Journal of Materials Chemistry A 2015 vol. 3(Issue 16) pp:3297-3305
Publication Date(Web):27 Feb 2015
DOI:10.1039/C4TB01984A
Ideal drug delivery systems should have prolonged circulation in blood, high accumulation in tumors with fast cellular uptake and burst drug release in cancer cells. Herein, a pH-sensitive small-molecule phospholipid prodrug based on phosphorylcholine (PC) was designed to overcome these challenges. The prodrug was synthesized by conjugating doxorubicin (DOX) to 11-mercaptoundecyl phosphorylcholine via an acid-labile hydrazone linker (UnPC-hyd-DOX). This phospholipid prodrug can self-assemble into core–shell micelles with exact and very high drug loading content (56.2%). Interestingly, the PC prodrug micelles can strongly minimize nonspecific phagocytosis by macrophages. They exhibited better ability to be internalized by cancer cells than that of the PEG prodrug micelles, which indicated that the PC shell facilitated cancer cell internalization. Moreover, in vitro results further demonstrated that DOX of phospholipid prodrug micelles can effectively escape from endo/lysosomes to the cytosol and enter the nucleus. An in vivo study demonstrated that these PC prodrug micelles exhibited much lower cardiotoxicity than free DOX. Importantly, PC prodrug micelles showed significantly slower blood clearance than PEG prodrug micelles and free DOX.
Co-reporter:Li-mei Wang, Hao Chang, He Zhang, Ke-feng Ren, Huan Li, Mi Hu, Bo-chao Li, M. Cristina L. Martins, Mário A. Barbosa and Jian Ji
Journal of Materials Chemistry A 2015 vol. 3(Issue 38) pp:7546-7553
Publication Date(Web):19 Aug 2015
DOI:10.1039/C5TB01151E
The stiffness of the substrates has been found to have a strong effect on cell behaviors, especially on cell adhesion, which is the first cellular event when cells contact materials. Much effort has been made to develop the materials with controlled stiffness for regulating cell adhesion. However, most available strategies for controlling the stiffness of material surfaces are generally limited to be static, which means that the stiffness is fixed during cell adhesion. Herein, we developed polyelectrolyte multilayer films (PEMs), and their stiffness can be dynamically modulated by mild stimuli. The PEMs were made by alternative deposition of poly-L-lysine (PLL) and thiol group modified hyaluronan (HA-SH) using the layer-by-layer assembly technique. The (PLL/HA-SH) multilayers can be cross-linked via oxidation of thiol groups. After crosslinking, the stiffness was increased and the adhesion of fibroblast cells was promoted. The stiffness of the multilayer films can be down-regulated dynamically by adding glutathione (GSH) in the medium, leading to in situ reduction of cell adhesion. Our study provides a promising strategy for the development of material surfaces with dynamically changeable stiffness, which is of great potential in the field of cell-based biomaterials.
Co-reporter:Haijie Han, Qiao Jin, Jian Ji
Journal of Controlled Release 2015 Volume 213() pp:e37
Publication Date(Web):10 September 2015
DOI:10.1016/j.jconrel.2015.05.059
Co-reporter:Yin Wang, Jianwei Du, Youxiang Wang, Qiao Jin and Jian Ji
Chemical Communications 2015 vol. 51(Issue 14) pp:2999-3002
Publication Date(Web):19 Jan 2015
DOI:10.1039/C4CC09274K
A novel type of dual pH-responsive supramolecular prodrug micelles based on host–guest interactions of water-soluble pillar[5]arene (WP5) and methyl viologen functioned doxorubicin (MV-DOX) was prepared. It was found that the prodrug micelles could be aggregated upon acidic condition, which led to enhanced accumulation and better therapy effect.
Co-reporter:Dan-dan Li, Xia-chao Chen, Ke-feng Ren and Jian Ji
Chemical Communications 2015 vol. 51(Issue 9) pp:1576-1578
Publication Date(Web):28 Oct 2014
DOI:10.1039/C4CC07899C
A pseudo-polycation was prepared based on the supramolecular cucurbit[8]uril ternary complex. It was then layer-by-layer assembled with poly(acrylic acid) to fabricate a stimuli-responsive film, which exhibited disassembly properties in response to stimuli, providing a supramolecular route for the fabrication of free-standing thin films.
Co-reporter:Haijie Han, Qiao Jin, Yin Wang, Yangjun Chen and Jian Ji
Chemical Communications 2015 vol. 51(Issue 98) pp:17435-17438
Publication Date(Web):05 Oct 2015
DOI:10.1039/C5CC06654A
An enzyme and reduction-activatable gemcitabine prodrug (TPE-GEM-RGD) with aggregation-induced emission (AIE) properties was designed for targeted and image-guided cancer therapy. TPE-GEM-RGD was successfully used for intracellular light-up imaging and glutathione (GSH)-responsive release of gemcitabine to suppress pancreatic cancer cells.
Co-reporter:Fan Jia, Yin Wang, Haibo Wang, Qiao Jin, Tongjiang Cai, Yangjun Chen and Jian Ji
Polymer Chemistry 2015 vol. 6(Issue 11) pp:2069-2075
Publication Date(Web):07 Jan 2015
DOI:10.1039/C4PY01420K
Ideal drug delivery systems are required to be stable in circulation, while instable at targeted sites to induce rapid drug release. To address this dilemma, novel light cross-linkable and pH de-cross-linkable micelles were developed as drug nanocarriers. Poly(ethylene glycol)-poly-(hydrazone umbelliferone)-aspartamide (mPEG-OMC) with light responsive coumarin moieties and pH responsive hydrazone groups in the side chains was synthesized. The polymers can self-assemble into micelles, which can be conveniently stabilized via UV-light induced cross-linking based on the dimerization of coumarin moieties. While under slight acidic conditions, the cross-linked micelles can also be de-cross-linked by the cleavage of hydrozone bonds in the cross-linking segments, accelerating the release of encapsulated drugs. Thus the benefits of pH and light stimuli-responsiveness can be combined and their disadvantages are avoided. The doxorubicin-loaded micelles showed high mortality towards HepG2 cells. We have demonstrated the UV light cross-linkable micelles with pH-triggered de-cross-linking properties as a new approach for designing smart drug delivery systems.
Co-reporter:Gongyan Liu, Quanqing Luo, Haiqi Gao, Yuan Chen, Xing Wei, Hong Dai, Zongcai Zhang and Jian Ji
Biomaterials Science 2015 vol. 3(Issue 3) pp:490-499
Publication Date(Web):22 Dec 2014
DOI:10.1039/C4BM00385C
In cancer therapy, surface engineering of drug delivery systems plays an essential role in their colloidal stability, biocompatibility and prolonged blood circulation. Inspired by the cell membrane consisting of phospholipids and glycolipids, a zwitterionic phosphorylcholine functionalized chitosan oligosaccharide (PC-CSO) was first synthesized to mimic the hydrophilic head groups of those amphipathic lipids. Then hydrophobic stearic acid (SA) similar to lipid fatty acids was grafted onto PC-CSO to form amphiphilic PC-CSO-SA copolymers. Cell membrane-mimetic micelles with a zwitterionic surface and a hydrophobic SA core were prepared by the self-assembly of PC-CSO-SA copolymers, showing excellent stability under extreme conditions including protein containing media, high salt content or a wide pH range. Doxorubicin (DOX) was successfully entrapped into polymeric micelles through the hydrophobic interaction between DOX and SA segments. After fast internalization by cancer cells, sustained drug release from micelles to the cytoplasm and nucleus was achieved. This result suggests that these biomimetic polymeric micelles may be promising drug delivery systems in cancer therapy.
Co-reporter:Hao Chang, He Zhang, Mi Hu, Xia-chao Chen, Ke-feng Ren, Jin-lei Wang and Jian Ji
Biomaterials Science 2015 vol. 3(Issue 2) pp:352-360
Publication Date(Web):08 Dec 2014
DOI:10.1039/C4BM00321G
In-stent restenosis and thrombosis are the main severe problems that occur after the percutaneous vascular intervention. The competition between endothelial cells (ECs) and smooth muscle cells (SMCs) plays a key role during these pathological changes. The regulation of this competition offers new opportunities to design biomaterials in the cardiovascular fields. Bioactive molecules have been typically employed to increase EC adhesion and thereafter to enhance EC competitiveness; however, this method is associated with limitations from the point of view of practical and industrial applications. Herein, we present an approach to enhance EC competitiveness over that of SMC through the selective EC adhesion, which is achieved by modulating a complex surface stiffness based on the technique of layer-by-layer (LbL) assembly. This complex stiffness can be achieved by regulating the thickness of multilayer films coordinating with a rigid underlying substrate. The selective cell adhesion is attributed to changes in the complex surface stiffness and a different intrinsic property between ECs and SMCs. This study provides a facile and broadly applicable approach for the purpose of the enhancement of EC competitiveness over that of SMC, which has great potential for the development of cell-based functional biomaterials in the cardiovascular field.
Co-reporter:Hao Chang;Ke-feng Ren;He Zhang;Jin-lei Wang;Bai-liang Wang
Journal of Biomedical Materials Research Part B: Applied Biomaterials 2015 Volume 103( Issue 2) pp:430-439
Publication Date(Web):
DOI:10.1002/jbm.b.33224
Abstract
Vascular gene-eluting stents (GES) is a promising strategy for treatment of cardiovascular disease. Very recently, we have proved that the (protamine sulfate/plasmid DNA encoding hepatocyte growth factor) (PrS/HGF-pDNA) multilayer can serve as a powerful tool for enhancing competitiveness of endothelial cell over smooth muscle cell, which opens perspectives for the regulation of intercellular competitiveness in the field of interventional therapy. However, before the gene multilayer films could be used in vascular stents for real clinical application, the preservation of gene bioactivity during the industrial sterilization and the hemocompatibility of film should be taken into account. Actually, both are long been ignored issues in the field of gene coating for GES. In this study, we demonstrate that the (PrS/HGF-pDNA) multilayer film exhibits the good gene-protecting abilities, which is confirmed by using the industrial sterilizations (gamma irradiation and ethylene oxide) and a routine storage condition (dry state at 4°C for 30 days). Furthermore, hemocompatible measurements (such as platelet adhesion and whole blood coagulation) and antibacterial assays (bacteria adhesion and growth inhibition) indicate the good anticoagulation and antibacterial properties of the (PrS/HGF-pDNA) multilayer film. The in vivo preliminary data of angiography and histological analysis suggest that the (PrS/HGF-pDNA) multilayer coated stent can reduce the in-stent restenosis. This work reveals that the (PrS/HGF-pDNA) multilayer film could be a promising candidate as coating for GES, which is of great potential in future clinic application. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 103B: 430–439, 2015.
Co-reporter:He Zhang, Hao Chang, Li-mei Wang, Ke-feng Ren, M. Cristina L. Martins, Mário A. Barbosa, and Jian Ji
Biomacromolecules 2015 Volume 16(Issue 11) pp:
Publication Date(Web):October 19, 2015
DOI:10.1021/acs.biomac.5b01057
Endothelial-to-mesenchymal transition (EndMT), during which endothelial cells (ECs) transdifferentiate into mesenchymal phenotype, plays a key role in the development of vascular implant complications such as endothelium dysfunction and in-stent restenosis. Substrate stiffness has been confirmed as a key factor to influence EC behaviors; however, so far, the relationship between substrate stiffness and EndMT has been rarely studied. Here, ECs were cultured on the (poly(l-lysine)/hyaluronate acid) (PLL/HA) multilayer films with controlled stiffness for 2 weeks, and their EndMT behaviors were studied. We demonstrated that ECs lost their markers (vWf and CD31) in a stiffness-dependent manner even without supplement of growth factors, and the softer film favored the maintaining of EC phenotype. Further, induced by transforming growth factor β1 (TGF-β1), ECs underwent EndMT, as characterized by losing their typical cobblestone morphology and markers and gaining smooth muscle cell markers (α-smooth muscle actin and calponin). Interestingly, stronger EndMT was observed when ECs were cultured on the stiffer film. Collectively, our findings suggest that substrate stiffness has significant effects on EndMT, and a softer substrate is beneficial to ECs by keeping their phenotype and inhibiting EndMT, which presents a new strategy for surface design of vascular implant materials.
Co-reporter:Lin Wang, Ke-feng Ren, Hai-bo Wang, Yin Wang, Jian Ji
Colloids and Surfaces B: Biointerfaces 2015 Volume 125() pp:127-133
Publication Date(Web):1 January 2015
DOI:10.1016/j.colsurfb.2014.11.017
•Doxorubicin (DOX) was conjugated onto the HA through pH-responsive hydrazone bond.•A multilayers was constructed by layer-by-layer assembly of PLL and HA-DOX.•The release of DOX from the multilayers was pH-dependent.•The (PLL/HA-DOX) multilayers showed the inhibition properties for cancer cells.Controlled and stimulated release of small drug molecules from polyelectrolyte multilayers is still a challenge due to the limitations to incorporate and control the interactions between small molecules and multilayers. Herein we reported a facile method to fabricate polyelectrolyte multilayers with pH-sensitive controlled release of doxorubicin (DOX). A pH-responsive polyelectrolyte was prepared by conjugating DOX onto hyaluronan (HA) via pH-responsive hydrazone bond with an 8% grafting degree. The HA-DOX was then incorporated into the multilayers via the layer-by-layer assembly with poly-l-lysine (PLL). The growth of the multilayers was tracked by spectroscopic ellipsometry. The morphology and structure of the films were characterized by scanning electron microscopy and UV–vis spectroscopy, respectively. The in vitro drug release experiments indicated that the release of DOX was pH-dependent: there was almost no release at pH 7.4, while the releases were significantly promoted at pH 6.0 and 5.0. Furthermore, human hepatoma (HepG2) cells were remarkably inhibited under the conditions at pH 5.0 when they were cultured with the (HA-DOX/PLL) multilayers. The multilayers with the properties of pH-sensitive DOX release would be potentially applied to the biomedical devices for tumor treatments.
Co-reporter:Lin Wang, Yin Wang, Qiao Jin, Fan Jia, Haibo Wang, Jian Ji
Polymer 2015 Volume 76() pp:237-244
Publication Date(Web):12 October 2015
DOI:10.1016/j.polymer.2015.09.003
•Hyaluronic acid prodrugs with pH and reduction responsiveness were prepared.•The prodrug can form remarkable micelles with a narrow size distribution.•The micelles could accumulate at the tumor site actively.•The prodrug system can inhibit the proliferation of the cancer cells effectively.Biomimic hyaluronic acid (HA) prodrug micelles with pH and reduction responsiveness were prepared by chemical graft of phosphorylcholine and doxorubicin (DOX) to the backbone of HA. DOX was conjugated to HA by pH-sensitive hydrazone bonds which could be hydrolyzed under acidic conditions and thus resulted in controlled release of DOX. Besides, the HA prodrug micelles were cross-linked via reduction-responsive disulfide bonds to improve the stability of the micelles. The HA prodrug can form remarkable core–shell micelles with a quite narrow size distribution which was confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The in vitro drug release studies showed that there was a dramatic release under endosome pH (pH = 5.0) and reductive environment (10 mM of dithiothreitol) than that at normal physiological environment (pH = 7.4). Greater uptake of DOX from HA prodrug micelles was observed in the CD44 receptor highly expressed MDA-MB-231 cell line, compared to the results from the CD44-negative cell line, NIH3T3, which was demonstrated by the flow cytometry and fluorescence microscopy. The glutathione (GSH)-responsive behaviors were studied as well. The micelles showed higher cellular proliferation inhibition against glutathione monoester (GSH-OEt) pretreated MDA-MB-231 cells than that of the non-pretreated and buthionine sulfoximine (BSO) pretreated ones. These results suggested that such pH/reduction dual-responsive prodrug micelles may enhance the selective inhibition to cancer cells which exhibit higher levels of GSH concentration and provide favorable platforms for cancer therapy.
Co-reporter:Yi-Xin Sun;Ke-Feng Ren;Guo-Xun Chang;Yi-Xiu Zhao;Xiang-Sheng Liu
Science Bulletin 2015 Volume 60( Issue 10) pp:936-942
Publication Date(Web):2015 May
DOI:10.1007/s11434-015-0780-5
Based on the noncovalent functionalization of ferrocene-grafted polyethylenimine (PEI-Fc) and carbon nanotubes (CNTs), CNT bundles are exfoliated by PEI-Fc solution and thus form stable compounds PEI-Fc@CNTs, which is used to construct the PEI-Fc@CNTs/DNA multilayers through layer-by-layer assembly. The multilayers show a highly uniform and homogeneous characteristic, which significantly improve the electrical property of the multilayers. Upon the oxidation electrical potential, the ferrocene groups are switched from reduction state ([Fe(C5H5)2]) to oxidation state ([Fe(C5H5)2]+), leading to change of microenvironments’ charge density, resulting in swelling of the multilayers and a final degree of swelling of 37 % and the decrease of multilayer stiffness. We maintain that electrochemical control over the swelling behavior of multilayers could have important implications for responsive coatings of nanoscale devices, including mechanically tunable surfaces which are used to modulate cellular activities and control drug delivery.
Co-reporter:Yin Wang, Dandan Li, Haibo Wang, Yangjun Chen, Haijie Han, Qiao Jin and Jian Ji
Chemical Communications 2014 vol. 50(Issue 66) pp:9390-9392
Publication Date(Web):09 Jul 2014
DOI:10.1039/C4CC03978E
The first attempt of constructing pH responsive supramolecular prodrug micelles based on cucurbit[8]uril is reported. The obtained prodrug micelles are found to be able to inhibit proliferation of cancer cells. It is anticipated that this facile strategy may open a novel avenue for the development of multifunctional drug delivery systems.
Co-reporter:Xiangsheng Liu, Nan Huang, Huan Li, Haibo Wang, Qiao Jin, and Jian Ji
ACS Applied Materials & Interfaces 2014 Volume 6(Issue 8) pp:5657
Publication Date(Web):March 27, 2014
DOI:10.1021/am5001823
Gold nanorods (AuNRs), because of their strong absorption of near-infrared (NIR) light, are very suitable for in vivo photothermal therapy of cancer. However, appropriate surface modification must be performed on AuNRs before their in vivo application because of the high toxicity of their original stabilizer cetyltrimethylammonium bromide. Multidentate ligands have attracted a lot of attention for modification of inorganic nanoparticles (NPs) because of their high ligand affinity and multifunctionality, while the therapeutic effect of multidentate ligands modified NPs in vivo remains unexplored. Here, we modified AuNRs with a polythiol PEG-based copolymer. The multidentate PEG coated AuNRs (AuNR-PTPEGm950) showed good stabilities in high saline condition and wide pH range. And they had much stronger resistance to ligand competition of dithiothreitol (DTT) than AuNRs coated by monothiol-anchored PEG. The AuNR-PTPEGm950 had very low cytotoxicity and showed high efficacy for the ablation of cancer cells in vitro. Moreover, the AuNR-PTPEGm950 showed good stability in serum, and they had a long circulation time in blood that led to a high accumulation in tumors after intravenous injection. In vivo photothermal therapy showed that tumors were completely cured without reoccurrence by one-time irradiation of NIR laser after a single injection of these multidentate PEG modified AuNRs.Keywords: cancer NIR photothermal therapy; gold nanorods; multidentate polyethylene glycol; surface modification; tumor accumulation;
Co-reporter:Huan Li, Xiangsheng Liu, Nan Huang, Kefeng Ren, Qiao Jin, and Jian Ji
ACS Applied Materials & Interfaces 2014 Volume 6(Issue 21) pp:18930
Publication Date(Web):October 6, 2014
DOI:10.1021/am504813f
The acidic microenvironment of tumor tissues has proven to be one of the major differences from other normal tissues. The near-infrared (NIR) light irradiation of aggregated gold nanoparticles in a tumor acidic pH-induced manner could then provide an effect approach to treat solid tumors with the advantage of minimizing the undesired damage to normal tissues. Although it is well-known the aggregation of larger nanoparticles will result in a better NIR photothermal effect, the preparation of pH-sensitive gold nanoparticles in large sizes remains a big challenge because of their worse dispersive stability. In this paper, we introduce a facile way to endow large gold nanoparticles with tunable pH-aggregation behaviors by modifying the nanoparticle surface with mixed-charge self-assembly monolayers compromising positively and negatively charged thiol ligands. Four different size nanoparticles were used to study the general principle of tailoring the pH-induced aggregation behaviors of mixed-charge gold nanoparticles (MC-GNPs) by adjusting the surface ligand composition. With proper surface ligand composition, the MC-GNPs in four different sizes that all exhibited aggregation at tumor acidic pH were obtained. The biggest MC-GNPs showed the most encouraging aggregation-enhanced photothermal efficacy in vitro when they formed aggregates. The mixed-charge self-assembled monolayers were then proved as a facile method to design pH-induced aggregation of large gold nanoparticles for better NIR photothermal cancer therapy.Keywords: mixed-charge gold nanoparticles; near-infrared (NIR) photothermal therapy; pH-induced aggregation; size effect
Co-reporter:Haibo Wang, Yin Wang, Yangjun Chen, Qiao Jin and Jian Ji
Polymer Chemistry 2014 vol. 5(Issue 3) pp:854-861
Publication Date(Web):09 Sep 2013
DOI:10.1039/C3PY00861D
A biodegradable and endosomal pH-sensitive polymeric prodrug poly(5-methyl-5-allyloxycarbonyl-1,3-dioxan-2-one)-graft-12-acryloyloxy dodecyl phosphorylcholine-co-6-maleimidocaproyl-doxorubicin (PMAC-graft-(ADPC-co-Mal-DOX) was synthesized by ring-opening polymerization (ROP) and “click” reaction. DOX was conjugated to the polymer by hydrazone bonds which would result in a pH-sensitive controlled release of drug. The polymeric prodrug can form a self-assembled micellar structure which was confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Flow cytometry and fluorescence microscopy results demonstrated that prodrug micelles could be internalized by cancer cells remarkably. In vitro drug release studies showed that the release of DOX was faster at endosomal pH (pH = 5.0) than at normal physiological environment (pH = 7.4). Moreover, this prodrug exhibited high cytotoxicity against HepG2 cells and HeLa cells, indicating its great potential for cancer therapy.
Co-reporter:Qiao Jin, Tongjiang Cai, Yin Wang, Haibo Wang, and Jian Ji
ACS Macro Letters 2014 Volume 3(Issue 7) pp:679
Publication Date(Web):July 2, 2014
DOI:10.1021/mz500290s
In this letter, light-responsive protein-encapsulated polyion complex (PIC) micelles were prepared by self-assembly of cationic block copolymer poly(N,N-dimethyl-N-(2-(methacryloyloxy)ethyl)-N-((2-nitrobenzyl)oxy)-2-oxoethanaminium bromide)-block-poly(carboxybetaine methacrylate) (PDMNBMA-b-PCBMA) and negatively charged bovine serum albumin (BSA). The PIC micelles were well characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). From the zeta potential measurement, the increase of the zeta potential of PIC micelles from ∼10 to ∼20 mV was observed when the solution pH decreased from 7.4 to 6.5, which could enhance the intracellular protein delivery efficiency. Moreover, the positively charged PDMNBMA blocks can be transformed to zwitterionic carboxybetaine units under UV irradiation, which could result in the disassembly of the PIC micelles. The release of BSA can therefore be drastically accelerated in the presence of UV irradiation. Meanwhile, the circular dichroism (CD) spectroscopy confirmed that the secondary structure of BSA was unaffected during the UV irradiation process.
Co-reporter:Xiangsheng Liu;Huan Li;Yangjun Chen;Qiao Jin;Kefeng Ren
Advanced Healthcare Materials 2014 Volume 3( Issue 9) pp:1439-1447
Publication Date(Web):
DOI:10.1002/adhm.201300617
Mixed-charge zwitterionic surface modification shows great potential as a simple strategy to fabricate nanoparticle (NP) surfaces that are nonfouling. Here, the in vivo fate of 16 nm mixed-charge gold nanoparticles (AuNPs) is investigated, coated with mixed quaternary ammonium and sulfonic groups. The results show that mixed-charge AuNPs have a much longer blood half-life (≈30.6 h) than do poly(ethylene glycol) (PEG, = 2000) -coated AuNPs (≈6.65 h) and they accumulate in the liver and spleen far less than do the PEGylated AuNPs. Using transmission electron microscopy, it is further confirmed that the mixed-charge AuNPs have much lower uptake and different existing states in liver Kupffer cells and spleen macrophages one month after injection compared with the PEGylated AuNPs. Moreover, these mixed-charge AuNPs do not cause appreciable toxicity at this tested dose to mice in a period of 1 month as evidenced by histological examinations. Importantly, the mixed-charge AuNPs have higher accumulation and slower clearance in tumors than do PEGylated AuNPs for times of 24–72 h. Results from this work show promise for effectively designing tumor-targeting NPs that can minimize reticuloendothelial system clearance and circulate for long periods by using a simple mixed-charge strategy.
Co-reporter:Jie Zhao, Chaojian Chen, Dandan Li, Xiangsheng Liu, Haibo Wang, Qiao Jin and Jian Ji
Polymer Chemistry 2014 vol. 5(Issue 6) pp:1843-1847
Publication Date(Web):10 Dec 2013
DOI:10.1039/C3PY01538F
A truly novel strategy for fabricating reducible supramolecular assemblies based on the host–guest interaction between cucurbit[8]uril (CB[8]) and methyl viologen (MV) is reported. The anticancer drug doxorubicin is loaded into the assemblies and a reducing agent Na2S2O4 can be used to successfully trigger release of drugs because of the redox chemistry of MV.
Co-reporter:Tongjiang Cai, Yangjun Chen, Yin Wang, Haibo Wang, Xiangsheng Liu, Qiao Jin, Seema Agarwal and Jian Ji
Polymer Chemistry 2014 vol. 5(Issue 13) pp:4061-4068
Publication Date(Web):25 Mar 2014
DOI:10.1039/C4PY00259H
Functional 2-methylene-1,3-dioxepane (MDO) terpolymers were explored here as a versatile platform to construct biodegradable pH sensitive polymeric prodrugs for intracellular drug delivery. A series of MDO-based biodegradable functional polyester P(MDO-co-PEGMA-co-PDSMA) with different compositions were synthesized by terpolymerization of MDO, poly(ethylene glycol) methyl ether methacrylate (PEGMA) and pyridyldisulfide ethylmethacrylate (PDSMA) via a simple one-pot radical ring-opening copolymerization. Mal-DOX, which contains a pH-sensitive hydrazone bond between doxorubicin (DOX) and the maleimide group, was covalently conjugated in one pot to free thiol groups of PDSMA units via thiol–ene click chemistry in the presence of tri(2-carboxyethyl)phosphine (TCEP). The DOX-conjugated P(MDO-co-PEGMA-co-PDSMA) can self-assemble into prodrug micelles. The diameter and morphology of the polymeric prodrug micelles were measured by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Because of the existence of the pH-sensitive hydrazone bonds, in vitro drug release results showed that the release of DOX was much faster at pH 5.5 than that at pH 7.4. Flow cytometry and fluorescence microscopy demonstrated that the prodrug micelles could be efficiently internalized by cancer cells. In vitro cytotoxicity showed that the DOX-conjugated prodrug micelles can strongly inhibit the proliferation of cancer cells remarkably. Importantly, this work provides a versatile strategy for the fabrication of biodegradable polymeric prodrug nanocarriers.
Co-reporter:Qiao Jin;Tongjiang Cai;Haijie Han;Haibo Wang;Yin Wang
Macromolecular Rapid Communications 2014 Volume 35( Issue 15) pp:1372-1378
Publication Date(Web):
DOI:10.1002/marc.201400171
Co-reporter:Jin-lei Wang, Ke-feng Ren, Hao Chang, Shi-miao Zhang, Lie-jiang Jin and Jian Ji
Physical Chemistry Chemical Physics 2014 vol. 16(Issue 7) pp:2936-2943
Publication Date(Web):02 Dec 2013
DOI:10.1039/C3CP54354D
Thin organic films containing carbon nanotubes (CNTs) have received increasing attention in many fields. In this study, a robust thin superhydrophobic film has been created by using layer-by-layer assembly of the carbon nanotubes wrapped by poly(dopamine) (CNT@PDA) and poly(ethyleneimine) (PEI). UV-vis spectroscopy, ellipsometry, and quartz crystal microbalance with dissipation (QCM-D) measurements confirmed that the sequential deposition of PEI and CNT@PDA resulted in a linear growth of the (PEI–CNT@PDA) film. This thin film contained as much as 77 wt% CNTs. Moreover, a very stable and flexible free-standing (PEI–CNT@PDA) film could be obtained by employing cellulose acetate (CA) as a sacrificial layer. The film could even withstand ultrasonication in saturated SDS aqueous solution for 30 min. SEM observations indicated that the ultrathin film consisted of nanoscale interpenetrating networks of entangled CNTs and exhibited a very rough surface morphology. The (PEI–CNT@PDA) film turned superhydrophobic after being coated with a low-surface-energy compound. The superhydrophobic films showed excellent resistance against the adhesion of both platelets and Escherichia coli (E. coli). The (PEI–CNT@PDA) films and the proposed methodology may find applications in the area of medical devices to reduce device-associated thrombosis and infection.
Co-reporter:Gong-Yan Liu;Min Li;Cong-Shan Zhu;Qiao Jin;Zong-Cai Zhang
Macromolecular Bioscience 2014 Volume 14( Issue 9) pp:1280-1290
Publication Date(Web):
DOI:10.1002/mabi.201400162
A novel amphiphilic copolymer, poly (ethylene glycol)-graft-polyethyleneimine/amide (PEG-g-PEI/amide), is synthesized by grafting PEG and1,2-cis-Cyclohexanedicarboxylic anhydride onto the PEI. PEGylated polymeric micelles can be assembled from the amphiphilic copolymers with well-defined nano-sizes, and anti-cancer drugs are successfully loaded into micelle core formed by the amide. The amides with neighboring carboxylic acid groups exhibit pH-dependent hydrolysis and can reversibly shield the cationic charge of amine groups on the PEI, giving the micelles a charge-conversion property from negative to positive in acidic tumor tissue environment. Meanwhile, the cleavage of amide bonds at acidic pH also results in the disassembly of the micelle and pH-responsive drug release. These micelles are promising drug delivery systems due to their smart properties: PEGylation, suitable size, charge-conversion, and simultaneous pH-sensitive drug release.
Co-reporter:Yi-xiu Zhao, Ke-feng Ren, Yi-xin Sun, Zi-jun Li and Jian Ji
RSC Advances 2014 vol. 4(Issue 47) pp:24511-24517
Publication Date(Web):15 May 2014
DOI:10.1039/C4RA03309D
Electroconductive hydrogel (ECH) films have becoming more and more attractive in the field of electro-stimulated response systems and biosensors. Comparatively speaking, the thinner ECH films enable faster response to external stimuli. However, construction of thin ECH films with thickness at the nano-to-micrometer scale is challenging. In the present study, we reported a thin ECH film by in situ electropolymerization of pyrrole within the layer-by-layer (LbL) polyelectrolyte multilayers. Thin poly(L-lysine)/sodium hyaluronate (PLL/HA) multilayers were fabricated. Polypyrrole (PPy) was then prepared by in situ electropolymerization of pyrrole within the multilayers by the galvanostatic method. Chronopotentiometry and an electro-quartz crystal microbalance were used to follow the electropolymerization. The chemical and structural characteristics of the thin ECH film were extensively investigated. Electrical impedance spectroscopy and cyclic voltammetry measurements demonstrated that this (PLL/HA)@PPy film has good electroconductivity with impedance as low as 5 Ω. This thin ECH film could to be a highly desirable candidate for applications in implantable electro-related biomedical devices and biosensors.
Co-reporter:Lan Jia;Lingyun Xu;Zhaohui Wang;Jianping Xu
Chinese Journal of Chemistry 2014 Volume 32( Issue 1) pp:
Publication Date(Web):
DOI:10.1002/cjoc.201490000
Co-reporter:Lan Jia;Lingyun Xu;Zhaohui Wang;Jianping Xu
Chinese Journal of Chemistry 2014 Volume 32( Issue 1) pp:85-90
Publication Date(Web):
DOI:10.1002/cjoc.201300086
Abstract
In this paper a label-free fluorescent sensor for probing the interaction between heparin and protein was reported. Heparin, the bioactive polyanions, formed supramolecular assemblies with cationic surfactant cetyltrimethyl ammonium bromide (CTAB). The environment-dependent dye pyrene, encapsulated in hydrophobic interiors of the supramolecular assemblies worked as the fluorescence probe. Once the heparin-binding protein was added, competing interactions of protein with heparin would weaken the interaction between CTAB and heparin. As a result, the noncovalently sequestered pyrene would be released upon disassembly and the fluorescence of the released pyrene was subsequently decreased. The binding events were exemplified by protamine and Tat peptide, these processes were also verified by DLS and TEM. Such a strategy is appealing as organic synthesis was traded off against supramolecular assembly. This label-free fluorescent system is simple, selective, convenient, and can serve as a good complement to other existing methods, also this method has the potential for preprimary drug screening.
Co-reporter:Qiao Jin;Gongyan Liu
Chinese Journal of Chemistry 2014 Volume 32( Issue 1) pp:73-77
Publication Date(Web):
DOI:10.1002/cjoc.201300742
Abstract
A new supramolecular self-assembly approach to construct micelles and reverse micelles was reported. Double-hydrophilic block copolymers poly(ethylene oxide)-b-poly(N-isopropylacrylamide) (PEO-b-PNIPAAm) was synthesized via atom transfer radical polymerization (ATRP) using PEO macroinitiator. Because of the lower critical solution temperature (LCST) phase behavior of PNIPAAm, PEO-b-PNIPAAm block copolymers self-assembled to form PNIPAAm-core micelles at 40°C. The PNIPAAm-core micelles were disassembled to unimers when the temperature was decreased to 25°C. But the addition of α-cyclodextrins (α-CDs) could induce the formation of PNIPAAm-shell micelles because of the "channel-type" crystallities induced by PEO/α-CDs polyrotaxanes. The assembly and disassembly procedure of micelles and reverse micelles were investigated by dynamic light scattering (DLS), X-ray diffraction (XRD), 1H NMR and transmission electron microscopy (TEM).
Co-reporter:Tongjiang Cai;Yangjun Chen;Yin Wang;Haibo Wang;Xiangsheng Liu;Qiao Jin;Seema Agarwal
Macromolecular Chemistry and Physics 2014 Volume 215( Issue 19) pp:1848-1854
Publication Date(Web):
DOI:10.1002/macp.201400311
Co-reporter:Jin-lei Wang, Bo-chao Li, Zi-jun Li, Ke-feng Ren, Lie-jiang Jin, Shi-miao Zhang, Hao Chang, Yi-xin Sun, Jian Ji
Biomaterials 2014 35(27) pp: 7679-7689
Publication Date(Web):
DOI:10.1016/j.biomaterials.2014.05.047
Co-reporter:Qiao Jin, Yangjun Chen, Yin Wang, Jian Ji
Colloids and Surfaces B: Biointerfaces 2014 Volume 124() pp:80-86
Publication Date(Web):1 December 2014
DOI:10.1016/j.colsurfb.2014.07.013
•Introduction of the mechanism toward stealth zwitterionic drug nanocarriers.•Applications of zwitterionic drug nanocarriers for the delivery of chemotherapeutants, DNA and protein.•Zwitterions provide superior properties compared to PEG.Nanomaterials self-assembled from amphiphilic functional copolymers have emerged as safe and efficient nanocarriers for delivery of therapeutics. Surface engineering of the nanocarriers is extremely important for the design of drug delivery systems. Bioinspired zwitterions are considered as novel nonfouling materials to construct biocompatible and bioinert nanocarriers. As an alternative to poly(ethylene glycol) (PEG), zwitterions exhibit some unique properties that PEG do not have. In this review, we highlight recent progress of the design of drug nanocarriers using a zwitterionic strategy. The possible mechanism of stealth properties of zwitterions was proposed. The advantages of zwitterionic drug nanocarriers deriving from phosphorylcholine (PC), carboxybetaine (CB), and sulfobetaine (SB) are also discussed.
Co-reporter:Yin Wang, Haibo Wang, Yangjun Chen, Xiangsheng Liu, Qiao Jin, Jian Ji
Colloids and Surfaces B: Biointerfaces 2014 Volume 121() pp:189-195
Publication Date(Web):1 September 2014
DOI:10.1016/j.colsurfb.2014.06.024
•A new β-CD based prodrug molecule was synthesized.•A facile way to address dual stimuli in cancer cells (endosomal pH and over produced H2O2) was proposed and realized by orthogonal assembly of β-CD-hydrazone-DOX and PEG-Fc.•The supramolecular prodrug micelles developed could be potentially used as nanocarriers for drug delivery.Nowadays, cancer is one of the most fatal threatens to human health. By utilizing the differences of cell environment between cancer cells and their normal counterparts as assembly-disassembly triggers, various smart drug nanocarriers have been designed to fight the cancer. Nevertheless, most of them are still not robust enough. One important reason is that they merely focus on a single stimulus. Thus, in order to achieve a better therapeutic effect, constructing multi responsive polymers is of great significance. However, most of multi responsive polymers used, up until now, are mainly based on block polymers synthesized via traditional polymerization methods, which are relatively time-consuming and laborious. Here in this article, a facile strategy preparing smart polymers with dual responsiveness (endosomal pH and over produced H2O2) was proposed and realized by orthogonal assembly of β-CD-hydrazone-DOX and PEG-Fc. The obtained polymers were found to be able to spontaneously assemble into micelles in water, indicating their potential applications as drug nanocarriers. In vitro study revealed that the release of the encapsulated DOX was significantly enhanced by both H2O2 and low pH at 5.0. Furthermore, fluorescence microscopy and flow cytometry analysis showed that the assembled supramolecular prodrug micelles could be internalized into cancer cells. These properties suggested their promising application in cancer therapy.
Co-reporter:Qiao Jin, Yin Wang, Tongjiang Cai, Haibo Wang, Jian Ji
Polymer 2014 Volume 55(Issue 18) pp:4641-4650
Publication Date(Web):2 September 2014
DOI:10.1016/j.polymer.2014.07.053
A novel amphiphilic photo-degradable hyperbranched polymer was reported at the first time. The hyperbranched o-nitrobenzyl containing poly(amino ester)s (HPAE) were prepared by one-pot Michael addition polymerization. The photo-induced degradation of hyperbranched poly(amino ester)s was confirmed by gel permeation chromatography (GPC) and UV-vis spectra. Bioinspired phosphorylcholine grafted HPAE (HPAE-PC) was synthesized via thiol-ene click chemistry. HPAE-PC can self-assemble to micelles and the micelles could be disassembled under UV irradiation because of the photo-degradation of HPAE. HPAE-PC micelles were used to load anticancer drug Doxorubicin (DOX). In vitro drug release studies showed that the release of DOX was much faster in the presence of UV irradiation than that without UV irradiation. The fluorescence microscope results indicated that DOX-loaded micelles exhibited faster drug release in A549 cells after UV irradiation. Moreover, the DOX-loaded HPAE-PC micelles under UV irradiation exhibited better anticancer activity against A549 cells than that of the nonirradiated ones. The novel amphiphilic photo-degradable hyperbranched polymers can be used to construct spatiotemporal on-demand drug delivery system for cancer therapy.
Co-reporter:Xiangsheng Liu, Haoyuan Huang, Gongyan Liu, Wenbo Zhou, Yangjun Chen, Qiao Jin and Jian Ji
Nanoscale 2013 vol. 5(Issue 9) pp:3982-3991
Publication Date(Web):13 Mar 2013
DOI:10.1039/C3NR00284E
Surface engineering of nanoparticles plays an essential role in their colloidal stability, biocompatibility and interaction with biosystems. In this study, a novel multidentate zwitterionic biopolymer derivative is obtained from conjugating dithiolane lipoic acid and zwitterionic acryloyloxyethyl phosphorylcholine to the chitosan oligosaccharide backbone. Gold nanoparticles (AuNPs) modified by this polymer exhibit remarkable colloidal stabilities under extreme conditions including high salt conditions, wide pH range and serum or plasma containing media. The AuNPs also show strong resistance to competition from dithiothreitol (as high as 1.5 M). Moreover, the modified AuNPs demonstrate low cytotoxicity investigated by both MTT and LDH assays, and good hemocompatibility evaluated by hemolysis of human red blood cells. In addition, the intracellular fate of AuNPs was investigated by ICP-MS and TEM. It showed that the AuNPs are uptaken by cells in a concentration dependent manner, and they can escape from endosomes/lysosomes to cytosol and tend to accumulate around the nucleus after 24 h incubation but few of them are excreted out of the cells. Gold nanorods are also stabilized by this ligand, which demonstrates robust dispersion stability and excellent hemocompatibility. This kind of multidentate zwitterionic chitosan derivative could be widely used for stabilizing other inorganic nanoparticles, which will greatly improve their performance in a variety of bio-related applications.
Co-reporter:Yi-xin Sun, Ke-feng Ren, Jin-lei Wang, Guo-xun Chang, and Jian Ji
ACS Applied Materials & Interfaces 2013 Volume 5(Issue 11) pp:4597
Publication Date(Web):May 20, 2013
DOI:10.1021/am401088w
Stimuli-responsive thin films attract considerable attention in different fields. Herein, an electrochemical redox multilayers with tunable stiffness is constructed through the layer-by-layer self-assembly method. The redox ferrocene modified poly(ethylenimine) play an essential role to induce multilayers’ swelling/shrinking under an electrochemical stimulus, resulting reversible change of elastic modulus of the multilayers. The adhesion of fibroblast cells can be thus controlled from well spreading to round shape. Such soft multilayers with electrochemically controlled stiffness could have potentials for cell-based applications.Keywords: cell adhesion; electrochemical redox; ferrocene; layer-by-layer self-assembly; stiffness; stimuli-responsive films;
Co-reporter:Bai-liang Wang, Ke-feng Ren, Hao Chang, Jin-lei Wang, and Jian Ji
ACS Applied Materials & Interfaces 2013 Volume 5(Issue 10) pp:4136
Publication Date(Web):April 19, 2013
DOI:10.1021/am4000547
Infections associated with medical devices have become a major concern. The adhesion of bacteria to the devices’ surfaces during the initial 24 h is believed to be a “decisive period” for implant-associated infections, which pose key challenges to optimal antiadhesion of microbes in this period. Herein, we have designed and constructed a (heparin/chitosan)10–(polyvinylpyrrolidone/poly(acrylic acid))10 [(HEP/CHI)10–(PVP/PAA)10] multilayer film by layer-by-layer self-assembly. Assembly of the underlying (HEP/CHI)10 multilayer film is based on electrostatic interactions, showing the properties of contact killing of bacteria. Deposition of the top (PVP/PAA)10 multilayer film is based on hydrogen bond interactions. The PAA molecules are then cross-linked to form anhydride groups by thermal treatment at 110 °C for 16 h. Therefore, it shows a top-down degradable capability in the determined period, leading to almost no adhesion of bacteria in 24 h. Our system combining the adhesion resistance and the contact killing properties shows an enhanced antibacterial capability through targeting the “decisive period” of implantation may have great potential for applications in medical implants, tissue engineering, etc.Keywords: antibacterial; degradable; implant-associated infections; layer-by-layer self-assembly; poly(acrylic acid); thermal cross-linking;
Co-reporter:Yin Wang, Haibo Wang, Yangjun Chen, Xiangsheng Liu, Qiao Jin and Jian Ji
Chemical Communications 2013 vol. 49(Issue 64) pp:7123-7125
Publication Date(Web):04 Jul 2013
DOI:10.1039/C3CC43687J
For the first time, pseudopolyrotaxane prodrug micelles with high drug content were prepared in water, which could be used for cancer therapy. It is anticipated that this facile strategy may open a novel avenue for the development of multifunctional drug delivery systems.
Co-reporter:Haibo Wang, Fangming Xu, Yin Wang, Xiangsheng Liu, Qiao Jin and Jian Ji
Polymer Chemistry 2013 vol. 4(Issue 10) pp:3012-3019
Publication Date(Web):01 Mar 2013
DOI:10.1039/C3PY00139C
The pH-triggered biodegradable micelles based on poly(β-amino ester)-graft-12-acryloyloxy dodecyl phosphorylcholine (PAE-graft-ADPC) were explored as an efficient acid-triggered anticancer drug delivery system. A pH-responsive biodegradable polymer was synthesized by using hydrophilic 12-acryloyloxy dodecyl phosphorylcholine (ADPC) and poly(β-amino ester) (PAE) via Michael addition reaction. Micelles with phosphorylcholine shells were prepared in aqueous solution and doxorubicin (DOX) was loaded into the core of the micelles with high efficiency (73%). Dynamic light scattering (DLS) and transmission electron microscopy (TEM) demonstrated that the size of the drug-loaded micelles was about 230 nm. DOX-loaded micelles were stable in the physiological environment, whereas they disassembled at pH 6.5 which is similar to the extracellular pH of most tumors. In vitro drug release showed that DOX release from micelles was faster at pH 6.5 than at 7.4. Intracellular uptake demonstrated that DOX was delivered into the cells effectively after the cells were incubated with DOX-loaded micelles at pH 6.5. Moreover, an in vitro cytotoxicity study indicated that the growth of HepG2 cells was inhibited remarkably when the cells were preincubated with DOX-loaded micelles at pH 6.5. The results indicated that the pH-triggered biodegradable micelles could serve as promising drug carriers for cancer therapy.
Co-reporter:Xiangsheng Liu;Huiguang Zhu;Qiao Jin;Wenbo Zhou;Vicki L. Colvin
Advanced Healthcare Materials 2013 Volume 2( Issue 2) pp:352-360
Publication Date(Web):
DOI:10.1002/adhm.201200210
Abstract
Facile surface modification of quantum dots (QDs) to make them water-soluble, small, stable, antibiofouling, and functional is crucial for their biological applications. This study demonstrates a simple ligand-exchange reaction to convert hydrophobic CdSe/ZnS QDs into water-soluble QDs using amphiphilic, zwitterionic 11-mercaptoundecylphosphorylcholine (HS-PC). The phosphorylcholine (PC)-modified QDs (QD-PC) possess several advantages, such as small hydrodynamic diameter, good resistance to pH variations and high salinity, excellent stabiliy in 100% human plasma, and low protein adsorption. Importantly, the PC modification endows the QDs with very low, nonspecific interaction with cells, and strongly minimizes nonspecific phagocytosis of QDs by macrophages. In addition, cell penetrating Tat peptide functionalized QDs can be easily produced by mixing Tat with HS-PC with various ratios, which is proved to effectively enhance QD ability to enter cells and accumulate around perinuclear region. Compared to traditional mercaptoundecanoic acid (MUA) modification, PC modification not only makes the cell penetrating QDs more stable and brighter, but also provides the Tat- and PC-conjugated QDs with much lower nonspecific phagocytic uptake than the Tat- and MUA-conjugated ones. This research will provide insights into designing suitable ligands for surface modification of QDs and improving biofunctional QD performance in biological applications.
Co-reporter:Haibo Wang, Fangming Xu, Dandan Li, Xiangsheng Liu, Qiao Jin and Jian Ji
Polymer Chemistry 2013 vol. 4(Issue 6) pp:2004-2010
Publication Date(Web):07 Jan 2013
DOI:10.1039/C2PY20981K
Efficient delivery systems should be stable in blood circulation, with efficient cellular uptake and rapid drug release in cancer cells. Herein, we synthesized P(2-(methacryloyloxy)-ethyl phosphorylcholine)-b-P(2-methoxy-2-oxoethyl methacrylate) via atom transfer radical polymerization. Doxorubicin (DOX) was linked to the polymer via a pH-responsive hydrazone bond. The polymer prodrug had high DOX content (10.6 wt%) and was able to self-assemble to form core–shell structured micelles. Dynamic light scattering showed that the average size of the micelles was 142.3 nm, which is the ideal size for the enhanced permeability and retention (EPR) effect. The shell of the micelles was composed of phosphorylcholine, which imitated the structure of cell membranes. Studies of intracellular uptake demonstrated that the prodrug micelles were internalized effectively by cancer cells. An in vitro release study indicated that the release of DOX at pH 5.0 was much faster than that at pH 7.4. Moreover, in vitro cytotoxicity showed that this polymer prodrug inhibited the growth of cancer cells remarkably, demonstrating its potential for use as an efficient drug delivery system.
Co-reporter:Chao-Jian Chen, Dan-Dan Li, Hai-Bo Wang, Jie Zhao and Jian Ji
Polymer Chemistry 2013 vol. 4(Issue 2) pp:242-245
Publication Date(Web):14 Sep 2012
DOI:10.1039/C2PY20549A
Biocompatible and dual-responsive micelles were fabricated from a cucurbit[8]uril (CB[8]) connected amphiphilic linear-hyperbranched polymer complex. After addition of adamantaneamine or Na2S2O4, the micelles became larger and exhibited triggered-release of hydrophobic coumarin 102 because of the CB[8]-based host–guest interaction.
Co-reporter:Jin-Lei Wang;Ke-Feng Ren;Hao Chang;Fan Jia;Bo-Chao Li;Ying Ji
Macromolecular Bioscience 2013 Volume 13( Issue 4) pp:483-493
Publication Date(Web):
DOI:10.1002/mabi.201200390
Co-reporter:Yin Wang;Haibo Wang;Gongyan Liu;Xiangsheng Liu;Qiao Jin
Macromolecular Bioscience 2013 Volume 13( Issue 8) pp:1084-1091
Publication Date(Web):
DOI:10.1002/mabi.201300052
Abstract
Poly(D,L-lactide)-SS-poly(2-methacryloyloxyethyl phosphorylcholine) block copolymers conjugated with cholesterol are synthesized by ROP and ATRP using a novel kind of double-dead initiator. This facile strategy not only can endue block copolymers with disulfide bonds, but can also overcome the disadvantages inherent in the synthesis procedure for the copolymers. The resultant biomimetic copolymers can self-assemble into near-monodisperse micelles. Subsequently, they are used as a carrier to encapsulate a hydrophobic dye, and the release can be triggered by a redox reagent, dithiothreitol. MTT study shows that the as-prepared micelles has good biocompatibility to both normal and cancer cells. These properties indicate that these micelles may be used as promising drug delivery vehicles.
Co-reporter:Jin-Lei Wang;Ke-Feng Ren;Hao Chang;Fan Jia;Bo-Chao Li;Ying Ji
Macromolecular Bioscience 2013 Volume 13( Issue 4) pp:
Publication Date(Web):
DOI:10.1002/mabi.201370011
Co-reporter:Yi-xin Sun, Ke-feng Ren, Yi-xiu Zhao, Xiang-sheng Liu, Guo-xun Chang, and Jian Ji
Langmuir 2013 Volume 29(Issue 35) pp:11163-11168
Publication Date(Web):2017-2-22
DOI:10.1021/la402378g
An electrochemically controlled drug release from a redox-active multilayer film is reported. The multilayer film is fabricated by alternate assembly of the electrochemical redox-active micelles and DNA. The buildup of multilayer films is monitored by spectroscopic ellipsometry, UV–vis spectroscopy, and fluorescence spectroscopy. A ferrocene-modified poly (ethyleneimine) (PEI-Fc) is used to form a hydrophobic ferrocene core and hydrophilic PEI shell micelle, showing the electrochemical redox-active properties. Hydrophobic pyrene (Py) molecules are then incorporated into the micelles. The PEI-Fc@Py micelles are assembled into the (PEI-Fc@Py/DNA) multilayer film by layer-by-layer assembly. Thanks to ferrocene groups with the properties of the hydrophilic-to-hydrophobic switch based on the electrical potential trigger, pyrene molecules can be control released from the multilayer film. The electrochemically controlled release of pyrene is investigated and confirmed by electrochemical quartz crystal microbalance and electrochemistry workstation. The (PEI-Fc@drug/DNA) multilayer film may have potential applications in the field of biomedical and nanoscale devices.
Co-reporter:Xiangsheng Liu, Jieming Cao, Huan Li, Jianyu Li, Qiao Jin, Kefeng Ren, and Jian Ji
ACS Nano 2013 Volume 7(Issue 10) pp:9384
Publication Date(Web):September 8, 2013
DOI:10.1021/nn404117j
Bioinspired polydopamine (PDA) has served as a universal coating to nanoparticles (NPs) for various biomedical applications. However, one remaining critical question is whether the PDA shell on NPs is stable in vivo. In this study, we modified gold nanoparticles (GNPs) with finely controlled PDA nanolayers to form uniform core/shell nanostructures (GNP@PDA). In vitro study showed that the PDA-coated GNPs had low cytotoxicity and could smoothly translocate to cancer cells. Transmission electron microscopy (TEM) analysis demonstrated that the PDA nanoshells were intact within cells after 24 h incubation. Notably, we found the GNP@PDA could partially escape from the endosomes/lysosomes to cytosol and locate close to the nucleus. Furthermore, we observed that the PDA-coated NPs have very different uptake behavior in two important organs of the liver and spleen: GNP@PDA in the liver were mainly uptaken by the Kupffer cells, while the GNP@PDA in the spleen were uptaken by a variety of cells. Importantly, we proved the PDA nanoshells were stable within cells of the liver and spleen for at least six weeks, and GNP@PDA did not show notable histological toxicity to main organs of mice in a long time. These results provided the direct evidence to support that the PDA surface modification can serve as an effective strategy to form ultrastable coatings on NPs in vivo, which can improve the intracellular delivery capacity and biocompatibility of NPs for biomedical application.Keywords: biocompatibility; biodistribution; biostability; cellular uptake; nanoparticles; polydopamine (PDA)
Co-reporter:Xiangsheng Liu, Yangjun Chen, Huan Li, Nan Huang, Qiao Jin, Kefeng Ren, and Jian Ji
ACS Nano 2013 Volume 7(Issue 7) pp:6244
Publication Date(Web):June 25, 2013
DOI:10.1021/nn402201w
Effective accumulation of nanoparticles (NPs) in tumors is crucial for NP-assisted cancer diagnosis and treatment. With the hypothesis that aggregation of NPs stimulated by tumor microenvironment can be utilized to enhance retention and cellular uptake of NPs in tumors, we designed a smart NP system to evaluate the effect of aggregation on NPs’ accumulation in tumor tissue. Gold nanoparticles (AuNPs, ∼16 nm) were facilely prepared by surface modification with mixed-charge zwitterionic self-assembled monolayers, which can be stable at the pH of blood and normal tissues but aggregate instantly in response to the acidic extracellular pH of solid tumors. The zwitterionic AuNPs exhibited fast, ultrasensitive, and reversible response to the pH change from pH 7.4 to pH 6.5, which enabled the AuNPs to be well dispersed at pH 7.4 with excellent stealth ability to resist uptake by macrophages, while quickly aggregating at pH 6.5, leading to greatly enhanced uptake by cancer cells. An in vivo study demonstrated that the zwitterionic AuNPs had a considerable blood half-life with much higher tumor accumulation, retention, and cellular internalization than nonsensitive PEGylated AuNPs. A preliminary photothermal tumor ablation evaluation suggested the aggregation of AuNPs can be applied to cancer NIR photothermal therapy. These results suggest that controlled aggregation of NPs sensitive to tumor microenvironment can serve as a universal strategy to enhance the retention and cellular uptake of inorganic NPs in tumors, and modifying NPs with a mixed-charge zwitterionic surface can provide an easy way to obtain stealth properties and pH-sensitivity at the same time.Keywords: aggregation; gold nanoparticles; mixed-charge zwitterionic; pH-responsive; tumor accumulation
Co-reporter:Fangming Xu, Haibo Wang, Jie Zhao, Xiangsheng Liu, Dandan Li, Chaojian Chen, and Jian Ji
Macromolecules 2013 Volume 46(Issue 11) pp:4235-4246
Publication Date(Web):June 3, 2013
DOI:10.1021/ma400276u
Although the most commonly reported low molecular weight hydrogelators (LMWG) are based on the strong and highly directional hydrogen bond between polar groups, the expansion of novel species of LMWG is quite necessary to fulfill different requirements of practical applications. Herein, we demonstrated that using an inherently chiral group—cholesterol as the hydrophobic part is a quite effective strategy to get phosphocholine-based LMWG, in which strong hydrogen bonds cannot be directly formed. A series of phospholipid hydrogelators, in which hydrophilic phosphocholine was connected to the chiral hydrophobic cholesteryl group through an alkyl chain, were designed and synthesized. Cholesteryl group greatly promoted the formation of one-dimensional supramolecular structures: helical nanofibril, twisted nanoribbon, helical nanotube, and spindle shaped vesicles were formed, and they showed drastic variation with just simple minor change on the molecular structures. All of them can further organize into cross-linked three-dimensional networks and form hydrogels. The hydrophobic interaction between cholesteryl groups also greatly improved the performance of hydrogel.
Co-reporter:Yu Wei, Ying Ji, Lin-Lin Xiao, Quan-kui Lin, Jian-ping Xu, Ke-feng Ren, Jian Ji
Biomaterials 2013 34(11) pp: 2588-2599
Publication Date(Web):
DOI:10.1016/j.biomaterials.2012.12.036
Co-reporter:Hao Chang, Ke-feng Ren, Jin-lei Wang, He Zhang, Bai-liang Wang, Shan-mei Zheng, Yuan-yuan Zhou, Jian Ji
Biomaterials 2013 34(13) pp: 3345-3354
Publication Date(Web):
DOI:10.1016/j.biomaterials.2013.01.065
Co-reporter:Xiangsheng Liu, Nan Huang, Haibo Wang, Huan Li, Qiao Jin, Jian Ji
Biomaterials 2013 34(33) pp: 8370-8381
Publication Date(Web):
DOI:10.1016/j.biomaterials.2013.07.059
Co-reporter:Jie-kan Sun, Ke-feng Ren, Lei-ze Zhu, Jian Ji
Colloids and Surfaces B: Biointerfaces 2013 Volume 112() pp:67-73
Publication Date(Web):1 December 2013
DOI:10.1016/j.colsurfb.2013.07.044
•Nanocomplex is prepared by using polyethyleneimine-ferrocene, doxorubicin and DNA.•Multilayers are fabricated through layer-by-layer assembly of the nanocomplexes.•Doxorubicin release is triggered by oxidation of ferrocene.•Cells are transfected by the multilayers through the substrate-mediated mode.Co-delivery of drugs and genes has synergistic advantages in many fields such as cancer treatments. In this study, we present a multilayers for co-delivery of doxorubicin (DOX) and DNA. Ferrocene-modified polyethyleneimine (PEI-Fc) is synthesized, and it can form micelles in solution with ferrocene core and PEI shell. DOX and DNA are thus incorporated into the core and shell of the micelles, respectively, to form the PEI-Fc–DOX–DNA nanocomplexes. Such cationic nanocomplexes are used to construct multilayers through layer-by-layer assembly with negatively charged dextran sulfate (DS). We show that the multilayers can release DOX, and the release can be significantly enhanced in a hydrogen peroxide condition. Moreover, the multilayers have the ability to transfect cells through a substrate-mediated mode. The (PEI-Fc–DOX–DNA/DS) multilayers can be potentially applied to the biomedical devices for cancer treatment, regenerative medicine, etc.
Co-reporter:Xiangsheng Liu, Nan Huang, Huan Li, Qiao Jin, and Jian Ji
Langmuir 2013 Volume 29(Issue 29) pp:9138-9148
Publication Date(Web):July 1, 2013
DOI:10.1021/la401556k
With the development of nanotechnology and its application in biomedicine, studies on the interaction between nanoparticles and cells have become increasingly important. To understand the surface and size effects on cell interaction of nanoparticles, the cellular uptake behaviors of two series of gold nanoparticles (AuNPs) with both positively and negatively charged surfaces and sizes range from ∼16 to ∼58 nm were investigated in both phagocytic RAW 264.7 and nonphagocytic HepG2 cells. The internalization of AuNPs was quantified by ICP-MS, and the intracellular fate of NPs was evaluated by TEM analysis. The results showed that the AuNPs with positive surface charge have much higher cell internalization ability than those with negative surface charge in nonphagocytic HepG2 cells. However, the uptake extent of negatively charged AuNPs was similar with that of the positively charged AuNPs when in phagocytic RAW 264.7 cells. Among the tested size range, negatively charged AuNPs with a diameter of ∼40 nm had the highest uptake in both cells, while the positively charged AuNPs did not show a certain tendency. Intracellular TEM analysis demonstrated the different fate of AuNPs in different cells, where both the positively and negatively charged AuNPs were mainly trapped in the lysosomes in HepG2 cells, but many of them were localized in phagosomes when in RAW 264.7 cells. Cytotoxicity of these AuNPs was tested by both MTT and LDH assays, which suggested NP’s toxicity is closely related to the tested cell types besides the surface and size of NPs. It demonstrates that cell interaction between nanoparticles and cells is not only affected by surface and size factors but also strongly depends on cell types.
Co-reporter:Dan-dan Li, Ke-feng Ren, Hao Chang, Hai-bo Wang, Jin-lei Wang, Chao-jian Chen, and Jian Ji
Langmuir 2013 Volume 29(Issue 46) pp:14101-14107
Publication Date(Web):October 22, 2013
DOI:10.1021/la4033332
The design of positively charged ultrathin films for surface modification is of crucial importance for biomedical applications. Herein, we report the layer-by-layer assembly of pure positively charged ultrathin films based on the host–guest interaction of cucurbit[8]uril (CB[8]). Two positively charged poly(ethylenimine)s (PEI) functionalized with guest moieties methyl viologen (MV) and indole (ID) were alternately assembled with the formation of CB[8] ternary complex under basic conditions. The growth of the (PEI-MV@CB[8]/PEI-ID) films was monitored by spectroscopic ellipsometry and quartz crystal microbalance. The morphology and structure of the films were characterized by scanning electron microscopy and UV–vis spectroscopy, respectively. These positively charged (PEI-MV@CB[8]/PEI-ID) films were very stable in the pH range from 4 to 9 but disassembled immediately when subjected to a competitive guest adamantylamine. Finally, the films were successfully employed as nanocontainers for DNA loading and subsequent directing the transfection of the adhered cells.
Co-reporter:Lina Chen, Haibo Wang, Yuanfeng Zhang, Youxiang Wang, Qiaoling Hu, Jian Ji
Colloids and Surfaces B: Biointerfaces 2013 Volume 111() pp:297-305
Publication Date(Web):1 November 2013
DOI:10.1016/j.colsurfb.2013.06.021
•Phosphorylcholine modification improved colloid stability and reduced cytotoxicity.•Bioinspired polyplexes were selectively uptaked by liver cancer cells.•Phosphorylcholine-modified polyplexes showed high transfection in cancer cells.We demonstrated here that the phosphorylcholine-modified polyplexes can be explored as effective gene vector for selective uptake and high transfection of cancer cells. 12-acryloyloxy dodecyl phosphorylcholine modified polyethyleneimine (PEI–ADPC) with grafting level about 13%, 8.3% and 4.5% was successfully synthesized. Gel retardation assay indicated that ADPC modification did not affect the DNA condensation ability. The PEI–ADPC13%/DNA and PEI–ADPC8.3%/DNA polyplexes were under 100 nm with a beneficial neutral surface at N/P ratio of 30. Sufficient ADPC shell endowed the polyplexes with high colloidal stability and low cytotoxicity. Compared to PEGylated polyplexes, it was interesting to find out that the PEI–ADPC/DNA polyplexes were selectively uptaked by liver cancer HepG2 cells. At the presence of chloroquine to exclude the limitation of lysosome escape, the ADPC-modified polyplexes showed more effective gene transfection in cancer cells than in normal cells because of the selective cell uptake. In conclusion, the convenient PC-modification modality was found to have both the function of biostability in the physiological environment and targetability toward cancer cells uniquely, which might have great potential use in cancer gene therapy.
Co-reporter:Wenbo Zhou, Xiangsheng Liu and Jian Ji
Journal of Materials Chemistry A 2012 vol. 22(Issue 28) pp:13969-13976
Publication Date(Web):12 Jun 2012
DOI:10.1039/C2JM16713A
Dual functionalization of gold nanorods (GNRs) with two kinds of surface ligands has been achieved. Phosphorylcholine (PC) could impart the GNRs with both biostability in the physiological environment and targetability towards cancer cells uniquely. On the other hand, the protein transduction domain of human immunodeficiency virus type 1 Tat peptide could induce the GNRs to be quickly internalized through cell membranes. The inductively coupled plasma mass spectroscopy (ICP-MS), TEM and UV-Vis assays all demonstrated that such dual-ligand GNRs exhibited both fast and selective cancer cell uptake advantages, which were utilized for more efficient cancer cell ablation under near-infrared (NIR) irradiation. This mode of the multivalent scaffold offers an optimized choice for future cell-based therapies.
Co-reporter:Gong-Yan Liu, Chao-Jian Chen, Dan-Dan Li, Shan-Shan Wang and Jian Ji
Journal of Materials Chemistry A 2012 vol. 22(Issue 33) pp:16865-16871
Publication Date(Web):18 Jul 2012
DOI:10.1039/C2JM00045H
Near-infrared light-sensitive polymeric micelles were prepared for the enhanced intracellular delivery of doxorubicin (DOX). The micelles were prepared from dextran-graft-(2-diazo-1,2-naphthoquinone) (Dex-DNQ) amphiphilic copolymers which were synthesized by modification of hydrophilic dextran with hydrophobic DNQ molecules. The hydrophobic DNQ molecule is an attractive photo-trigger group because its UV/NIR-induced Wolff rearrangement can result in a drastic change into a hydrophilic 3-indenecarboxylic acid (3-IC) molecule with pKa of 4.5. Thus, under UV or NIR irradiation, Dex-DNQ micelles will rapidly release encapsulated drugs due to the micelle dissociation. DOX was chosen as an anticancer drug to be encapsulated into the Dex-DNQ micelle with the loading efficiency and content of 60% and 24%, respectively. In vitro cell viability studies, the micelles exhibited higher intracellular DOX release under NIR irradiation at 808 nm, which resulted in significant growth inhibition of HepG2 cancer cells. Fluorescence microscopy and flow cytometry further proved the enhanced intracellular drug release behaviour of DOX-loaded Dex-DNQ micelles under NIR irradiation. We are convinced that this smart drug nanocarrier is potentially useful for cancer chemotherapy.
Co-reporter:Xiangsheng Liu, Qiao Jin, Ying Ji and Jian Ji
Journal of Materials Chemistry A 2012 vol. 22(Issue 5) pp:1916-1927
Publication Date(Web):06 Dec 2011
DOI:10.1039/C1JM14178C
Gold nanoparticles (AuNPs) with excellent resistance to phagocytic uptake by macrophages are achieved via a facile mixed charged zwitterionic self-assembled monolayers (SAMs) surface modification. A series of AuNPs with good dispersity against high salinity, strong resistance to plasma adsorption, persistent stability in cell culture medium and low cytotoxicity are prepared by surface modification with mixed charged SAMs in relatively wide range ratios of oppositely charged thiols. An in vitro study demonstrates that AuNPs modified by mixed charged SAMs effectively minimize the nonspecific cell uptake by either non-phagocytic HUVEC and HepG2 cells or phagocytic RAW 264.7 cells. When different factors that affect cell uptake including incubation time, nanoparticles concentration and incubation mode were evaluated, all results demonstrated that the resistance to phagocytosis by macrophage RAW 264.7 of the zwitterionic AuNPs is even much better than that of the traditional PEGylated AuNPs. A hemolysis assay with human erythrocytes demonstrates the good blood biocompatibility of the zwitterionic AuNPs. The excellent “stealth” properties of the mixed charged AuNPs promise their further biomedical applications both in vitro and in vivo.
Co-reporter:Liyan Shen, Bailiang Wang, Jinlei Wang, Jinhong Fu, Catherine Picart, and Jian Ji
ACS Applied Materials & Interfaces 2012 Volume 4(Issue 9) pp:4476
Publication Date(Web):September 4, 2012
DOI:10.1021/am301118f
A superhydrophobic/hydrophilic asymmetric free-standing film has been created using layer-by-layer assembly technique. Poly(ethylene-imine)-Ag+ complex (PEI-Ag+) at pH 9.0 was assembled with poly(acrylic acid) (PAA) at pH 3.2 on a Teflon substrate to yield a micronanostructured surface that can be turned to be superhydrophobic after being coated with a low surface energy compound. Silver nanoparticle loaded free-standing film with one surface being superhydrophobic while the other surface is hydrophilic was then obtained after detachment from the substrate. The superhydrophobicity enabled the upper surface with anti-adhesion and self-cleaning properties and the hydrophilic bottom surface can release silver ions as antibiotic agent. The broad-spectrum antimicrobial capability of silver ions released from the bottom surface coupled with superhydrophobic barrier protection of the upper surface may make the free-standing film a new therapy for open wound.Keywords: anti adhesion; asymmetric; drug release; free-standing films; layer-by-layer assembly; superhydrophobic;
Co-reporter:Liyan Shen, Laetitia Rapenne, Patrick Chaudouet, Jian Ji, Catherine Picart
Journal of Colloid and Interface Science 2012 Volume 388(Issue 1) pp:56-66
Publication Date(Web):15 December 2012
DOI:10.1016/j.jcis.2012.06.079
In situ synthesis of inorganic nanoparticles (NPs) in polyelectrolytes multilayers (PEMs) has recently gained much attention. Due to the versatility of their composition, PEMs offer a unique opportunity to synthesize a variety of NPs. So far, mostly cationic precursors have been used and only few studies have investigated the possibility of using amine groups to bind anionic precursors. Here, we use exponentially growing poly(l-lysine)/hyaluronan (PLL/HA) films as a nanoreservoir to bind and sequester aurochlorate (AuCl4-) anions thanks to the large number of free amine groups. The polypeptide–polysaccharide reactive template enabled the formation in a spatially-confined environment of gold NP at a very high yield. The synthesized gold NPs were homogenous and well-dispersed in the nanocomposite. Importantly, there was no particular effect of the film-ending layer (either PLL or HA). The largest particles of ∼9 nm and the largest amount of gold were obtained at acidic pH of 3. When the pH was increased, smaller and more numerous NPs were synthesized but the total amount of gold was lower. Based on UV–visible spectrometry, FTIR and TEM data, we finally propose a scheme for the mechanism of gold NPs formation, in which several groups of PLL and HA contribute to the binding of gold ions, the nucleation and growth of NPs, and their stabilization in the “bulk” of the film.Graphical abstractHighlights► Poly(l-lysine)/hyaluronan (PLL/HA) films as nanoreservoir for aurochlorate anions. ► In situ, synthesis of gold nanoparticles (NPs) in a spatially-confined environment. ► Tunable size of gold NP from ∼2 nm to ∼9 nm, depending on the loading pH. ► Importance of specific functional groups revealed by FTIR spectroscopy. ► A scheme for the mechanism of gold NPs formation is proposed.
Co-reporter:Gong-Yan Liu, Chao-Jian Chen and Jian Ji
Soft Matter 2012 vol. 8(Issue 34) pp:8811-8821
Publication Date(Web):14 Jun 2012
DOI:10.1039/C2SM25721A
Biocompatible and biodegradable polymersomes are commonly self-assembled from amphiphilic diblock copolymers composed of hydrophilic poly(ethylene glycol) (PEG) or poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) segments and hydrophobic polyester blocks, such as poly(lactic acid) (PLA) or poly(ε-caprolactone) (PCL). Such polymersomes have emerged as promising delivery vehicles for pharmaceutical applications. Presented in this review are summaries of recent developments of biocompatible and biodegradable polymersomes, including self-assembly, encapsulation of various therapeutics, pH-induced hydrolysis for controlled release as well as their functionalization and intelligent design.
Co-reporter:Bai-Liang Wang, Xiang-Sheng Liu, Ying Ji, Ke-Feng Ren, Jian Ji
Carbohydrate Polymers 2012 Volume 90(Issue 1) pp:8-15
Publication Date(Web):1 September 2012
DOI:10.1016/j.carbpol.2012.03.080
Infection associated with medical devices is one of the most frequent complications of modern medical biomaterials. Preparation of antibacterial films on the medical devices is a great challenge owing to bactericidal efficiency, long acting and biocompatibility. In this study, silver nanoparticles (Ag NPs) doped chitosan/polyvinylpyrrolidone (PVP) films were successfully prepared by dip coating method. The nanocomposite films with spherical Ag NPs (diameters in 10–50 nm) were stable after being immersed in PBS for 35 days. Through regulating the concentration of AgNO3, the nanocomposite films showed good cell compatibility. The nanocomposite films could eliminate 100% Staphylococcus aureus (ATCC 6538) and Escherichia coli (ATCC 8739) in 5 min and had favorable long-acting antibacterial property. The increase of PVP amount obviously enhanced anti-adhesion activity of the nanocomposite film. Such nanocomposite films can be expected to have good potential in biomaterials applications.Highlights► CHI-Ag/PVP nanocomposite film prepared can release Ag+ at a controlled rate. ► Pretreatment of substrate enhanced the binding capacity of films in PBS buffer. ► Increasing PVP amount obviously reduce adhesion of bacteria. ► The film has little cytotoxicity as AgNO3 concentration is below 0.25 mM. ► The film exhibits strong and long-acting bactericidal activity towards bacteria.
Co-reporter:Ying Ji;Yu Wei;Xiangsheng Liu;Jinlei Wang;Kefeng Ren
Journal of Biomedical Materials Research Part A 2012 Volume 100A( Issue 6) pp:1387-1397
Publication Date(Web):
DOI:10.1002/jbm.a.34077
Abstract
Surface immobilization of bioactive molecules has been a promising strategy to develop in situ endothelialization for cardiovascular implants. With the aim to construct endothelial cell specific coating with low fouling property, zwitterionic carboxybetaine methacrylate and butyl methacrylate were copolymerized as coating materials, spin-coated onto substrates, and immobilized with endothelial cell selective peptide Arg-Glu-Asp-Val (REDV) through functionalization of carboxy groups in carboxybetaine by NHS/EDC chemistry. Experimental results proved that carboxybetaine-REDV coating maintained desirable antifouling ability and fine hemocompatibility. Separate culture and coculture of HUVECs (human umbilical vein endothelial cells) with HUASMCs (human umbilical artery smooth muscle cells) showed that the coating was able to enhance the competitive growth of endothelial cells while limiting the adhesion, proliferation, and migration of smooth muscle cells. The existence of zwitterionic carboxybetaine helps to screen undesirable adsorption of platelets, and its nonspecific resistance to smooth muscle cells contributes to the realization of endothelial cell selectivity. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 2012.
Co-reporter:Chao-Jian Chen, Gong-Yan Liu, Xiang-Sheng Liu, Dan-Dan Li and Jian Ji
New Journal of Chemistry 2012 vol. 36(Issue 3) pp:694-701
Publication Date(Web):15 Dec 2011
DOI:10.1039/C2NJ20882B
Photo-responsive micelles with reversible self-assembly and disassembly behaviours were constructed via the supramolecular host–guest interaction of β-cyclodextrin (β-CD) and an amphiphilic azobenzene-containing hyperbranched polymer (denoted HPHEEP-Azo). The polymer was prepared through the carboxylation of hydroxyl groups in hyperbranched polyphosphate (HPHEEP-OH) with succinic anhydride and the subsequent esterification reaction with 4-hydroxyazobenzene. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) measurements reveal that HPHEEP-Azo can self-assemble into spherical micelles with an average diameter of 169.9 nm in aqueous solution. The critical micelle concentration (CMC) of the micelles is 0.013 mg mL−1. After addition of β-CD into the micellar solution, the micelles dissociated gradually upon increasing the addition amount of β-CD. Irradiation experiments show that reversible self-assembly and disassembly behaviours can be controlled by irradiating with UV and visible light. These photo-responsive micelles self-assembled from hyperbranched polymers might have great potential in various practical applications such as controlled drug release.
Co-reporter:Jie-Kan Sun, Ke-Feng Ren, Jian Ji
Thin Solid Films 2012 Volume 520(Issue 16) pp:5426-5430
Publication Date(Web):1 June 2012
DOI:10.1016/j.tsf.2012.04.019
Development of materials with stimuli-responsive properties is of interest for biotechnical applications including gene delivery and regenerative medicine. Here, we report a multilayer film through layer-by-layer self-assembly of DNA polyplexes and charge-reversible poly(ethylenimine) (cPEI). Through functionalizing PEI with cyclohexanedicarboxylic acid, cPEI showed negatively charged and therefore was used for electrostatic self-assembly with positively charged DNA polyplexes. Side chains of cPEI can be hydrolyzed in acidic environment while it is stable in neutral condition. Such pH-triggered hydrolysis led to charge reverse of cPEI from negative to positive, which consequently led to a disassembly of multilayer film. Both UV–vis and ellipsometry spectrum measurements suggested that the multilayer film grew with a thickness of 150 nm for twelve bilayers. Under low pH condition, the multilayer film collapsed and DNA polyplexes were released. The multilayer film containing cPEI could be served as a local gene delivery system in specific low pH conditions such as extracellular acidity of solid tumor and lysosomal.Highlights► A charge-reversible poly(ethylenimine) (cPEI) was synthesized. ► cPEI can be hydrolyzed from negative to positive charge depending on pH. ► The (cPEI/DNA polyplexes) multilayer was fabricated via layer-by-layer deposition. ► pH-triggered hydrolysis of cPEI leads to a disassembly of multilayer film.
Co-reporter:Qiao Jin;Christoph Luy;Seema Agarwal
Journal of Polymer Science Part A: Polymer Chemistry 2012 Volume 50( Issue 3) pp:451-457
Publication Date(Web):
DOI:10.1002/pola.25050
Abstract
Multistimuli-responsive precise morphological control over self-assembled polymers is of great importance for applications in nanoscience as drug delivery system. A novel pH, photoresponsive, and cyclodextrin-responsive block copolymer were developed to investigate the reversible morphological transition from micelles to vesicles. The azobenzene-containing block copolymer poly(ethylene oxide)-b-poly(2-(diethylamino)ethyl methacrylate-co-6-(4-phenylazo phenoxy)hexyl methacrylate) [PEO-b-P(DEAEMA-co-PPHMA)] was synthesized by atom transfer radical polymerization. This system can self-assemble into vesicles in aqueous solution at pH 8. On adjusting the solution pH to 3, there was a transition from vesicles to micelles. The same behavior, that is, transition from vesicles to micelles was also realizable on addition of β-cyclodextrin (β-CD) to the PEO-b-P(DEAEMA-co-PPHMA) solution at pH 8. Furthermore, after β-CD was added, alternating irradiation of the solution with UV and visible light can also induce the reversible micelle-to-vesicle transition because of the photoinduced trans-to-cis isomerization of azobenzene units. The multistimuli-responsive precise morphological changes were studied by laser light scattering, transmission electron microscopy, and UV–vis spectra. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011
Co-reporter:Chao-Jian Chen, Qiao Jin, Gong-Yan Liu, Dan-Dan Li, Jin-Lei Wang, Jian Ji
Polymer 2012 Volume 53(Issue 17) pp:3695-3703
Publication Date(Web):2 August 2012
DOI:10.1016/j.polymer.2012.06.024
Reversibly light-responsive and biocompatible micelles with an appropriate size were constructed from an amphiphilic spiropyran-containing hyperbranched polyphosphate (denoted as HPHEEP-SP). The polymer was conveniently synthesized based on the modification of a biodegradable hyperbranched polyphosphate with carboxyl-containing spiropyran molecules. HPHEEP-SP can self-assemble to biocompatible micelles with an average diameter of 186.3 nm and a critical micelle concentration of 0.052 mg mL−1. After 5 min of UV irradiation, the diameter of the micelles decreased gradually to about 100 nm, which is ascribed to the transformation of hydrophobic spiropyran to hydrophilic merocyanine. Subsequent exposure the micelles to visible light, the diameter of the micelles was restored. Model drug coumarin 102 was then encapsulated into the micelles successfully. Light-controlled release and re-encapsulation behaviours were lastly demonstrated by fluorescence spectroscopy. This study provides a convenient way to construct smart nanocarriers for controlled release and re-encapsulation of hydrophobic drugs.Graphical abstract
Co-reporter:Shaopeng Pang, Congshan Zhu, Fangming Xu, Chaojian Chen, Jian Ji
Colloids and Surfaces B: Biointerfaces 2012 Volume 94() pp:22-26
Publication Date(Web):1 June 2012
DOI:10.1016/j.colsurfb.2012.01.006
Zirconium-phosphonate (Zr-P) ionic complexation chemistry is explored as a new approach to fabricate poly[2-(methacryloyloxy) ethyl phosphorylcholine] (PMPC) multilayer film by layer-by-layer self-assembly method. Quartz crystal microbalance with dissipation (QCM-D) and optical ellipsometry measurements demonstrated that PMPC layer can be fully absorbed on each Zr4+ layer. The thickness of the multilayer film with a good linear relationship was followed by the ellipsometry in situ adlayer characterization. The influence of pH of the PMPC and Zr4+ solutions on the multilayer deposition were investigated by optical ellipsometry. QCM-D results indicated that the multilayer film is stable in a PBS flowing chamber at a high flow rate of 5.2 × 10−3 m/s. The ellipsometry data demonstrated that 67.2% of the film still remained on the silicon wafer after being strong shaken in PBS at 80 rpm for 12 h. The adsorption of bovine serum albumin (BSA) and fetal bovine serum (FBS) on the PMPC surface was monitored by the QCM-D and spectroscopic ellipsometry, and the results showed the multilayer film have excellent protein resistance.Graphical abstractHighlights► We demonstrate an approach to fabricate PC multilayer via Zr-P ionic complexation. ► The pH has a considerable effect on the growth of the [PC/Zr4+]n multilayer film. ► The film exhibits good stability in the PBS buffer and protein resistance property.
Co-reporter:Quan-Kui Lin, Yue Hou, Ke-Feng Ren, Jian Ji
Thin Solid Films 2012 Volume 520(Issue 15) pp:4971-4978
Publication Date(Web):31 May 2012
DOI:10.1016/j.tsf.2012.03.041
Thrombosis and in-stent restenosis are the main obstacles in the healing process after cardiovascular surgery. A promising way to achieve the healing process after percutaneous transluminal coronary angioplasty followed by stenting may rely on the rapid in situ endothelialization on the materials of implants. Several requirements are raised to achieve in situ endothelialization, of which the specifically endothelial cells (ECs) homing and the non-specific cells repulsion come first. In this work, heparin/chitosan multilayer was constructed with thromboresistant and non-specifically cell-resistant properties. The specific ECs adhesive peptide sequence Arg-Glu-Asp-Val (REDV) was then immobilized onto the pristine multilayer and the cell responses of ECs and smooth muscle cells (SMCs) were verified. It is interesting that ECs selective attachment was obtained on the REDV functionalized multilayer, whereas the multilayer maintains resisting to the SMCs. These results show that the REDV functionalized cell-resistant heparin/chitosan multilayer is a ECs selective surface, which may have great potential in cardiovascular biomaterials for in situ endothelialization.Highlights► The (heparin/chitosan) multilayer was fabricated via layer-by-layer deposition. ► Native (heparin/chitosan) multilayer is cell-resistant. ► Chemistry-crosslinking converts the multilayer to a cells adhesive surface. ► Arg-Glu-Asp-Val peptide modified multilayer promotes endothelial cells adhesion.
Co-reporter:Gong-Yan Liu, Xiang-Sheng Liu, Shan-Shan Wang, Chao-Jian Chen, and Jian Ji
Langmuir 2012 Volume 28(Issue 1) pp:557-562
Publication Date(Web):November 10, 2011
DOI:10.1021/la2033669
For polymersomes to achieve their potential as effective delivery vehicles, they must efficiently encapsulate therapeutic agents into either the aqueous interior or the hydrophobic membrane. In this study, cell membrane-mimetic polymersomes were prepared from amphiphilic poly(d,l-lactide)-b-poly(2-methacryloyloxyethylphosphorylcholine) (PLA-b-PMPC) diblock copolymers and were used as encapsulation devices for water-soluble molecules. Thioalkylated zwitterionic phosphorylcholine protected quantum dots (PC@QDs) were chosen as hydrophilic model substrates and successfully encapsulated into the aqueous polymersome interior, as evidenced by transmission electron microscopy (TEM) and flow cytometry. In addition, we also found a fraction of the PC@QDs were bound to both the external and internal surfaces of the polymersome. This interesting immobilization might be due to the ion-pair interactions between the phosphorylcholine groups on the PC@QDs and polymersomes. The experimental encapsulation results support a mechanism of PLA-b-PMPC polymersome formation in which PLA-b-PMPC copolymer chains first form spherical micelles, then worm-like micelles, and finally disk-like micelles which close up to form polymersomes.
Co-reporter:Chaojian Chen, Gongyan Liu, Xiangsheng Liu, Shaopeng Pang, Congshan Zhu, Liping Lv and Jian Ji
Polymer Chemistry 2011 vol. 2(Issue 6) pp:1389-1397
Publication Date(Web):02 Apr 2011
DOI:10.1039/C1PY00094B
Photo-responsive biocompatible micelles were constructed from amphiphilic hyperbranched polyphosphate based polymer (denoted as HPHEEP-DNQ) and applied in the controlled release of coumarin 102. HPHEEP-DNQ was designed and synthesized by modification of hydrophilic hyperbranched polyphosphate (HPHEEP) with hydrophobic, light-responsive 2-diazo-1,2-naphthoquinone (DNQ) molecules. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) measurements revealed that the polymer can self-assemble into spherical micelles with an average diameter of about 186 nm in aqueous solution. The critical micelle concentration (CMC) of the micelles was 0.025 mg mL−1 determined by fluorescence spectroscopy using Nile Red as a fluorescence probe. By illuminating the micelles with 365 nm UV light, light triggered destabilization procedure was investigated by TEM and DLS. In addition, model drug coumarin 102 was successfully encapsulated into the micelles and the controlled release behavior under 365 nm UV light was investigated by fluorescence spectroscopy. Cell viability tests against two types of cells indicated that the micelles have excellent biocompatibility. These photo-responsive and biocompatible polymeric micelles self-assembled from hyperbranched polyphosphate based polymer might have great potential as smart carriers in the field of drug delivery.
Co-reporter:Chao-Jian Chen;Gong-Yan Liu;Ye-Ting Shi;Cong-Shan Zhu;Shao-Peng Pang;Xiang-Sheng Liu
Macromolecular Rapid Communications 2011 Volume 32( Issue 14) pp:1077-1081
Publication Date(Web):
DOI:10.1002/marc.201100196
Co-reporter:Gongyan Liu, Qiao Jin, Xiangsheng Liu, Liping Lv, Chaojian Chen and Jian Ji
Soft Matter 2011 vol. 7(Issue 2) pp:662-669
Publication Date(Web):22 Oct 2010
DOI:10.1039/C0SM00708K
Poly(ethylene oxide) (PEO) and poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) are biocompatible polymers that have delivered clinically proven benefits in various biomedical applications. Biocompatible polymer vesicles were prepared on basis of the inclusion complexation between α-cyclodextrins (α-CDs) and double-hydrophilic poly(ethylene oxide)-b-poly(2-methacryloyloxyethyl phosphorylcholine) (PEO-b-PMPC) in aqueous media without using organic solvent. The supramolecular structure of the nano-sized vesicles was demonstrated by transmission electron microscopy (TEM), atomic force microscopy (AFM) and dynamic light scattering (DLS). The biocompatibility of PEO-b-PMPC block copolymers and PEO-b-PMPC/α-CDs vesicles were studied by cell viability test, and the results revealed that both of them showed excellent cytocompatibility. Hydrophilic doxorubicin (DOX·HCl) was successfully loaded into the vesicle with loading content of 10.3% and loading efficiency of 30%. The DOX·HCl loaded vesicles showed lower cytotoxicity than free drugs, and could efficiently deliver and release the drug into HepG2 cells as confirmed by fluorescence microscope (FM). With these properties, the polymer vesicles are attractive as drug carriers for pharmaceutical applications.
Co-reporter:Congshan Zhu, Shaopeng Pang, Jianping Xu, Lan Jia, Fangming Xu, Ju Mei, Anjun Qin, Jingzhi Sun, Jian Ji and Benzhong Tang
Analyst 2011 vol. 136(Issue 16) pp:3343-3348
Publication Date(Web):13 Jul 2011
DOI:10.1039/C1AN15176B
The aggregation-induced emission (AIE) of a 1,2-diphenyl-1,2-di(p-tolyl)ethene (TPE) was explored as a novel fluorescence method for probing the assembling/disassembling of amphiphilic molecules. The fluorescence intensity was able to monitor the formation of micelles and determine the critical micelle concentration (CMC) of surfactants. The temperature-dependent micellization of the pharmaceutically important PEO–PPO–PEO copolymer, Pluronic F127, was further studied by using the TPE fluorescence spectrum intensity. Our results showed good agreement with those reported in the literature by using other methods. The special advantage of the AIE probe method was further explored to determine the assembling/disassembling process of the colored amphiphilic molecule, 1-[4-(3-phenylazophenoxy)butyl]triethylamine bromide (AzoC4), whose CMC value has not previously been described. Since the TPE fluorescence signal mainly comes from the aqueous phase, not from the inside of hydrophobic core, it provides a possible platform to study the CMC of those colored surfactants. Based on the novel fluorescence properties of TPE in the aggregated and dispersed states, one can conclude that the TPE method is a promising method for the determination of the CMC and critical micellization temperature (CMT), particularly having a special advantage to determine the assembling/disassembling process of colored amphiphilic molecules.
Co-reporter:Jian-Ping Xu, Yuan Fang, Zhe-Gang Song, Ju Mei, Lan Jia, An Jun Qin, Jing Zhi Sun, Jian Ji and Ben Zhong Tang
Analyst 2011 vol. 136(Issue 11) pp:2315-2321
Publication Date(Web):14 Apr 2011
DOI:10.1039/C0AN00813C
Herein, BSA–tetraphenylethene derivative conjugates with aggregation-induced emission (AIE) properties were constructed and used as fluorescent probes for label-free detection of protease and α1-antitrypsin. Conjugated AIE probes were formed based on the electrostatic induced assembly between an ammonium cation of quaternized tetraphenylethene salt and carboxyl anion groups of BSA. While water soluble quaternized tetraphenylethene salt showed very low fluorescence in its well-dispersed state, obvious enhancement in the fluorescence of the aggregated tetraphenylethene derivative on the BSA templates was achieved due to the abnormal aggregation-induced emission properties of tetraphenylethene. These BSA–tetraphenylethene derivative conjugates enabled label-free detection of protease. In the presence of trypsin, the BSA templates were enzymatically hydrolyzed and the conjugates decomposed. Therefore the quaternized tetraphenylethene molecules became increasingly isolated from each other. Accordingly, the aggregation to dispersing state change of tetraphenylethene derivative resulted in an obvious decrease in the fluorescence of the conjugates probes and enabled the sensitive and selective detection of trypsin. Furthermore, upon addition of α1-antitrypsin, the enzymatic activity of trypsin was inhibited and the fluorescence was consequently preserved. Sensitive detection of α1-antitrypsin was thus realised. The protein–tetraphenylethene derivative conjugates with aggregation-induced emission properties therefore show great promise for the monitoring of biological processes and cancer diagnostics with simplicity, high sensitivity, and rapid response.
Co-reporter:Gong-Yan Liu, Li-Ping Lv, Chao-Jian Chen, Xiang-Sheng Liu, Xiao-Fen Hu and Jian Ji
Soft Matter 2011 vol. 7(Issue 14) pp:6629-6636
Publication Date(Web):13 Jun 2011
DOI:10.1039/C1SM05308F
Nano-sized biocompatible and biodegradable polymersomes were prepared based on poly(D,L-lactide)-block-poly(2-methacryloyloxyethyl phosphorylcholine) (PLA-b-PMPC) diblock copolymers and applied for the release anti-cancer drugs. Hydrophobic doxorubicin (DOX) and hydrophilic doxorubicin hydrochloride (DOX·HCl) were successfully loaded into the polymersome membrane and polymersome interior, respectively. The in vitro release studies demonstrated that the release of DOX and DOX·HCl from polymersomes was highly pH-dependent, i.e. significantly faster drug release at mildly acidic pH of 5.0 compared to physiological pH 7.4. Furthermore, DOX·HCl-loaded polymersomes exhibited faster drug release than DOX-loaded polymersomes under the same pH conditions. The highly pH-depended release behavior was attributed to the hydrolysis of PLA-b-PMPC, which would result in morphological transformation from polymersome to micelle with a triggered release of the encapsulated drugs. The drug-loaded polymersomes were shown to rapidly enter HepG2 cells, localize in their endosome/lysosomes with acidic pH environment and display enhanced intracellular release of the drugs into the cytosol. These biocompatible and acid pH-sensitive polymersomes might have great potential for cancer therapy.
Co-reporter:Fang-Ming Xu, Jian-Ping Xu, Li-Ping Lv and Jian Ji
Soft Matter 2011 vol. 7(Issue 3) pp:1114-1120
Publication Date(Web):26 Nov 2010
DOI:10.1039/C0SM00763C
Polymeric supramolecular assemblies provide a simple and versatile approach to fabricate specific nanostructures and functional nanocomposites in recent years. However, only few supramolecular assembly morphologies, in most cases, micelles and vesicles, have been reported. Herein, novel bowl- and porous sphere-shaped supramolecular assemblies were prepared by self-assembly of a supramolecular copolymer which was formed through end group ionic interaction between hydrophilic poly(2-methacryloyloxyethyl phosphorylcholine) with amino end groups (PMPC-NH2) and hydrophobic polystyrene with carboxyl end groups (PSt-COOH). Furthermore, it is interesting to find that the electrostatic induced supramolecular assemblies possess great potential for further functionalization at the ionic combining interfaces. Gold nanoparticles with a weak positive charge on their surface were assembled in a series of supramolecular assemblies. It was important to note that the gold nanoparticles were preferentially located at the inner interface of the supramolecular assemblies, bowls, porous spheres and others. The present method might be promising to extend to other supramolecular and nanoparticle systems to build spatial distribution precisely controlled nanoparticle–polymer composites.
Co-reporter:Quankui Lin;Jiajie Yan;Fuyu Qiu;Xiaoxiao Song;Guosheng Fu
Journal of Biomedical Materials Research Part A 2011 Volume 96A( Issue 1) pp:132-141
Publication Date(Web):
DOI:10.1002/jbm.a.32820
Abstract
Endothelialization and antithrombogenicity are two key issues in stent implantation. The layer-by-layer (LbL) deposition of anticoagulant heparin and cell compatible collagen was explored to develop a multilayered coating with synergic property of antithrombogenicity and fast endothelialization. The quartz crystal microbalance with dissipation (QCM-D), UV spectrometer, spectroscopic ellipsometry, scanning electron microscopy, and confocal laser scanning microscopy investigations indicate that the LbL technique, which based on molecular assembly, provides an easy way to develop a smooth, homogenous, and stable coating onto stents. In vitro blood clotting time tests and the platelet adhesion tests show that the multilayer-modified stents present good hemocompatibility. In vitro endothelial cell (EC) culture results show that the multilayer-modified surfaces accelerate the adhesion and proliferation of ECs. These results illustrate that a stent surface coating with properties of antithrombogenicity and EC preference was obtained via heparin/collagen multilayer modification. This surface coating may have great potential in facilitating in situ endothelialization of blood contacting materials. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.
Co-reporter:Gong-Yan Liu;Li-Ping Lv;Chao-Jian Chen;Xiao-Fen Hu
Macromolecular Chemistry and Physics 2011 Volume 212( Issue 6) pp:
Publication Date(Web):
DOI:10.1002/macp.201000735
Co-reporter:Gongyan Liu;Xiaofen Hu;Chaojian Chen;Qiao Jin
Polymer International 2011 Volume 60( Issue 4) pp:
Publication Date(Web):
DOI:10.1002/pi.2981
Abstract
Biodegradable poly[(2-methacryloyloxyethyl phosphorylcholine)-block-(D,L-lactide)] (PMPC-b-PLA) diblock copolymers with various hydrophilic PMPC weight fractions (fPC) will spontaneously self-assemble into well-defined vesicles and large compound micelles (LCMs) in water. Transmission electron microscopy, scanning electron microscopy, dynamic light scattering and fluorescence microscopy were used to observe their aggregate morphologies. The degradation of the LCMs was investigated and the loss of molecular weight of PLA blocks was confirmed using 1H NMR analysis. The hydrolysis of PLA increases fPC and consequently shifts the preferred morphology from LCMs to vesicles. Such degradation-induced morphological transitions mean that the biocompatible and biodegradable LCMs have great application potential in drug delivery. Copyright © 2010 Society of Chemical Industry
Co-reporter:Yu Wei, Ying Ji, LinLin Xiao, QuanKui Lin, Jian Ji
Colloids and Surfaces B: Biointerfaces 2011 Volume 84(Issue 2) pp:369-378
Publication Date(Web):1 June 2011
DOI:10.1016/j.colsurfb.2011.01.028
Arg-Glu-Asp-Val (REDV) peptide with endothelial cells (ECs) selectivity was immobilized onto PEG based polymeric coating via the active p-nitrophenyloxycarbonyl group. The adhesion and proliferation of human umbilical vein endothelial cells (HUVECs) and human aortic smooth muscle cells (HASMCs) onto surface modified either by REDV end-tethered polyethylene glycol (PEG) or by the complex of free PEG and REDV were investigated to understand the synergic action of nonspecific resistance of PEG and specific recognitions of REDV. Cell culture results indicated that the surfaces end tethered by REDV peptide via PEG “spacer” (n = 1, 6, 10) exhibited slight EC selectivity and showed small difference between different lengths of PEG chain. Both separate-culture and co-culture of HUVECs and HASMCs indicated that the introducing of free PEG into REDV tethered surface inhibited HASMCs adhesion significantly and remained a high level of HUVECs growth. Furthermore, the surface with short free PEG chain (n = 6) was much more effective to enhance ECs selectivity than long EG chain (n = 23). The combination of nonspecific resistance of short free PEG and the ECs selectivity of REDV peptide presents much better ability to enhance the competitive adhesion of HUVECs over HASMCs.Graphical abstractResearch highlights► Two kinds of PEG based biomimetic copolymers containing tail like chain structure with active terminal group and random copolymer structure with free PEG chain are prepared. ► The surface coatings with two different structures containing PEG and REDV peptide exhibit good hemocompatibility. ► The surfaces end tethered REDV via PEG “spacer” (n = 1, 6, 10) exhibit slight EC selectivity and show little difference between different lengths of PEG “spacer” (n = 1, 6, 10). ► The combination of nonspecific resistance of short free PEG chain and the ECs selectivity of REDV (P(EG)6BN–REDV) presents much better ability enhancing the competitive growth of HUVECs and keep good HUVECs morphology over HASMCs.
Co-reporter:Lan Jia, Jian-Ping Xu, Hai Wang, Jian Ji
Colloids and Surfaces B: Biointerfaces 2011 Volume 84(Issue 1) pp:49-54
Publication Date(Web):1 May 2011
DOI:10.1016/j.colsurfb.2010.12.012
Biomimetic acryloyloxyethyl phosphorylcholine (APC) was used to react with generation 5 poly(amido amine) (PAMAM) dendrimers (G5) via the Michael addition reaction between primary amino group of PAMAM dendrimers and acrylic functional group of APC. FTIR and 1H NMR confirmed the success of surface modification of G5. The primary amino and phosphorylcholine (PC) group numbers of the surface engineered PAMAM dendrimers (G5-PC) were calculated to be 56 and 50 via 1H NMR and potentiometric titration. Cell viability and cell morphology studies indicated that biomimetic phosphorylcholine surface engineering successfully lowered the cytotoxicity of G5 PAMAM dendrimers. The hydrophobic interior of G5-PC was used to incorporate anti-cancer drug Adriamycin (ADR) and the G5-PC showed sustained releasing behavior for ADR. Cell morphology and viability tests indicated that the drug-loaded G5-PC conjugate could effectively enter the cancer cells and inhibit the growth of cancer cells. Biomimetic phosphorylcholine surface engineered PAMAM dendrimers with lowered cytotoxicity and high cellular penetrating ability showed great potential for the biomedical applications as nanocarrier system.Graphical abstractResearch highlights▶ PAMAM dendrimers (G5) were surface engineered by biomimetic phosphorylcholine (PC). ▶ The surface engineered PAMAM (G5-PC) efficiently lowered the cytotoxicity of G5. ▶ G5-PC showed sustained releasing behavior for anti-cancer drug ADR. ▶ G5-PC-ADR could effectively enter and inhibit the growth of the cancer cells.
Co-reporter:Xuefei Wang, Jiekan Sun, Jian Ji
Reactive and Functional Polymers 2011 71(3) pp: 254-260
Publication Date(Web):1 March 2011
DOI:10.1016/j.reactfunctpolym.2010.09.007
A rapid growth of the biodegradable multilayer of poly (l-lysine) (PLL) and DNA was constructed here by alternating deposition of PLL at high pH and DNA at low pH. The exponential growth rate of the multilayer was increased by increasing pH difference between the two deposition solutions. The pH modulated layer-by-layer method provides an easy and rapid way not only to elevate DNA dose in multilayer coating but also to modulate the ratio of PLL to DNA within multilayer coating. Relatively higher transfection levels were achieved for plasmid degraded from the PLL/plasmid 9.5/5.0 (PLL and plasmid were alternatively deposited at pH 9.5 and pH 5.0) and 10.0/4.6 (film was formed by alternative deposition of PLL at pH 10.0 and plasmid at pH 4.6) films when compared with that of PLL/plasmid 7.2/7.2 multilayer (PLL/plasmid film constructed both at pH 7.2). The film with more DNA and higher N/P ratio might provide a new method to enhance transfection in localized gene delivery system.
Co-reporter:Xiangsheng Liu, Haoyuan Huang, Qiao Jin, and Jian Ji
Langmuir 2011 Volume 27(Issue 9) pp:5242-5251
Publication Date(Web):April 8, 2011
DOI:10.1021/la2002223
Here we report a facile way of stabilizing large gold nanoparticles (AuNPs) by mixed charged zwitterionic self-assembled monolayers (SAMs). The citrate-capped AuNPs with diameters ranging from 16 nm to even ∼100 nm are well stabilized via a simple place exchange reaction with a 1:1 molar ratio mixture of negatively charged sodium 10-mercaptodecanesulfonic acid (HS-C10-S) and positively charged (10-mercaptodecyl)-trimethyl-ammonium bromide (HS-C10-N4). The 16 nm AuNPs protected by mixed charged zwitterionic SAMs not only show much better stability than the single negatively or positively charged AuNPs, but also exhibit exciting stability as well as those modified by monohydroxy (1-mercaptoundec-11-yl) tetraethylene glycol (HS-C11-EG4). Importantly, 16 nm AuNPs protected by mixed SAMs exhibit good stability in cell culture medium with 10% FBS and strong protein resistance, especially with excellent resistance against plasma adsorption. Moreover, the mixed charged zwitterionic SAMs are also able to well-stabilize larger AuNPs with a diameter of 50 nm, and to help remarkably improve their stability in saline solution compared with HS-C11-EG4 protected ones. When it comes to AuNPs with a diameter of 100 nm, the mixed charged zwitterionic SAM protected nanoparticles retain a smaller hydrodynamic diameter and even better long-term stability than those modified by mercaptopolyethylene glycol (Mw = 2000, HS-PEG2000). The above results demonstrated that the mixed charged zwitterionic SAMs are able to have a similar effect on stabilizing the large gold nanoparticles just like the single-component zwitterionic SAMs. Concerning its ease of preparation, versatility, and excellent properties, the strategy based on the mixed charged zwitterionic SAM protection might provide a promising method to surface tailoring of nanoparticles for biomedical application.
Co-reporter:Xiaofen Hu and Jian Ji
Biomacromolecules 2011 Volume 12(Issue 12) pp:
Publication Date(Web):November 4, 2011
DOI:10.1021/bm201137x
A convenient and simple route to multifunctional surface coatings via the alternating covalent layer-by-layer (LBL) assembly of p-nitrophenyloxycarbonyl group-terminated hyperbranched polyether (HBPO-NO2) and polyethylenimine (PEI) is described. The in situ chemical reaction between HBPO-NO2 and PEI onto aminolyzed substrates was rapid and mild. Results from ellipsometry measurements, contact angle measurements, and ATR–FTIR spectra confirmed the successful LBL assembly of the building blocks, and the surface reactivity of the multilayer films with HBPO-NO2 as the outmost layer was demonstrated by the immobilization of an amine-functionalized fluorophore. Furthermore, a biomimetic surface was achieved by surface functionalization of the multilayer films with extracellular matrix protein collagen to promote the adhesion and growth of cells. The studies on the drug loading and in vitro release behaviors of the multilayer films demonstrated their application potentials in local delivery of hydrophilic and hydrophobic therapeutic agents.
Co-reporter:Lan Jia, Jian-Ping Xu, Di Li, Shao-Peng Pang, Yuan Fang, Zhe-Gang Song and Jian Ji
Chemical Communications 2010 vol. 46(Issue 38) pp:7166-7168
Publication Date(Web):18 Aug 2010
DOI:10.1039/C0CC01244K
An alkaline phosphatase activity detection system was constructed based on the different quenching effect of the enzyme substrate and product on the β-CD-functionalized CdTe QDs.
Co-reporter:Wenbo Zhou, Jinyan Shao, Qiao Jin, Qingshan Wei, Jianguo Tang and Jian Ji
Chemical Communications 2010 vol. 46(Issue 9) pp:1479-1481
Publication Date(Web):19 Jan 2010
DOI:10.1039/B915125G
The conjugation of zwitterionic phosphorylcholine onto gold nanorods leads to enhanced and selective uptake within cancer cells.
Co-reporter:Qiao Jin, Gongyan Liu, Xiangsheng Liu and Jian Ji
Soft Matter 2010 vol. 6(Issue 21) pp:5589-5595
Publication Date(Web):09 Sep 2010
DOI:10.1039/C0SM00428F
An azobenzene-containing block copolymer poly(ethylene oxide)-b-poly(6-[4-phenylazo phenoxy]hexyl methacrylate-co-2-(dimethylamino)ethyl methacrylate) (PEO-b-P(AzoMA-co-DMAEMA)) was successfully designed to explore self-assembly behavior in an aqueous solution. PEO-b-P(AzoMA-co-DMAEMA) can self-assemble into vesicles in water. The morphologies and sizes of the vesicles can be controlled by copolymerization of hydrophobic AzoMA with different amounts of DMAEMA. Spherical vesicle-to-compound vesicle-to-irregular vesicle transitions were observed by facilely adjusting the content of DMAEMA and AzoMA. After the addition of different amounts of β-CD, vesicles were transformed into micelles and at last dissociated. Alternating irradiation of the solution with UV and visible light induced the reversible supramolecular self-assembly and disassembly of vesicles because of the photo-induced trans-to-cis isomerization of azobenzene units. The supramolecular self-assembly and disassembly procedure was studied by dynamic light scattering (DLS), transmission electron microscopy (TEM) and UV-vis spectra.
Co-reporter:Jian-Ping Xu, Zhe-Gang Song, Yuan Fang, Ju Mei, Lan Jia, An Jun Qin, Jing Zhi Sun, Jian Ji and Ben Zhong Tang
Analyst 2010 vol. 135(Issue 11) pp:3002-3007
Publication Date(Web):29 Sep 2010
DOI:10.1039/C0AN00554A
Herein, a sensitive and selective sensor for mercury(II) and glutathione based on the aggregation-induced emission (AIE) of a tetraphenylethene derivative stimulated by Hg2+-DNA complexes is reported. Aggregation complexes of AIE probes, quaternized tetraphenylethene salt and anti-Hg2+ aptamer ssDNA, were formed based on the electrostatic interactions between the ammonium cation of AIE probes and the backbone phosphate anions of DNA. In the presence of target Hg2+, the aptamer ssDNA with thymine (T)-rich sequences selectively bound with Hg2+ to form an Hg2+-bridged T base pair and the ssDNA changed into a hairpin-like structure. Therefore the AIE probing molecules were brought to be positioned closer. Accordingly, the conformational change of aptamer ssDNA resulted in an obvious enhancement in the fluorescence of the probing complex enabling the sensitive and selective detection of Hg2+. Furthermore, upon reaction of Hg2+ with biothiols, the compact structure was destroyed and the fluorescence decreased consequently. Sensitive detection of GSH was realised based on the decrease of fluorescence of the probing complex. The target-aptamer complexes stimulating aggregation-induced emission therefore show great promise for environmental and biological process monitoring and disease diagnosis.
Co-reporter:Leize Zhu, Yonggang Shangguan, Yixin Sun, Jian Ji and Qiang Zheng
Soft Matter 2010 vol. 6(Issue 21) pp:5541-5546
Publication Date(Web):09 Sep 2010
DOI:10.1039/C0SM00246A
Redox-responsive, hydrophobically associating polymers which can change their structures, conformations and properties through specific redox reaction are interesting, because they can be used to construct novel biosensors and can be applied to environmentally benign electro-functional systems, such as electrically switchable drug delivery systems and sol–gel materials. Studies on the rheological properties of these polymers are essential to realize their applications in these areas. Herein, rheological properties of redox-responsive ferrocene modified branched poly(ethylene imine) (BPEI-Fc) in aqueous solution were studied. The association behavior of this polymer during heating–cooling cycles and with the addition of NaCl was also explored. Viscometric measurements suggest the viscosity of this system can be markedly reduced by the introduction of β-cyclodextrin. 1H NMR results indicate inclusion compounds are formed between β-cyclodextrin and ferrocene. Moreover, hydrogen peroxide can be an alternative way to reduce the viscosity of BPEI-Fc solution as demonstrated by viscometric measurements and UV/Vis spectroscopy. With these outstanding properties, we expect this system may find wide applications in biosensors, drug delivery and electrically switchable materials.
Co-reporter:Jian-Ping Xu, Lan Jia, Yuan Fang, Li-Ping Lv, Zhe-Gang Song and Jian Ji
Analyst 2010 vol. 135(Issue 9) pp:2323-2327
Publication Date(Web):05 Jul 2010
DOI:10.1039/C0AN00217H
Highly soluble fluorescent pyrene derivative with substantially improved fluorescence intensity in aqueous buffer was obtained via PEGylation strategy. The highly soluble PEGylated pyrene (PEO-Py) non-covalently adsorbed onto the surface of gold nanoparticles (Au NPs) to form dyads with quenched fluorescence due to highly efficient energy transfer between PEO-Py and Au NPs. The PEO-Py/Au NPs dyads were used for the sensitive turn-on fluorescent detection of biothiols. The fluorescence of PEO-Py was restored by the addition of cysteine (Cys), indicating that Cys can modulate the energy transfer between PEO-Py and Au NPs. This phenomenon then allowed for the sensitive detection of Cys with a limit of detection (LOD) of 11.4 nM. The linear range of determination of Cys was from 1.25 × 10−8 to 2.25 × 10−7 M. None of the other amino acids found in proteins showed obvious interference with the determination. It was important to note that the detection sensitivity of the PEO-Py/Au NPs system was more than 5-fold improved compared with the Py/Au NPs system. In addition, other biothiol molecules, such as glutathione, could also be detected by this sensor system. The method was also successfully applied to the determination of the total content of aminothiols in human plasma. Therefore an easily prepared, inexpensive, high solubility fluorescent probe has been realized and is also expected to detect other biological analytes of interest.
Co-reporter:Qiao Jin, Gongyan Liu, Jian Ji
European Polymer Journal 2010 Volume 46(Issue 11) pp:2120-2128
Publication Date(Web):November 2010
DOI:10.1016/j.eurpolymj.2010.09.001
Reversibly photo-cross-linkable pH-responsive block copolymer poly(ethylene oxide)-b-poly((2-(diethylamino)ethyl methacrylate-co-4-methyl-[7-(methacryloyl)oxyethyloxy] coumarin)) (PEO-b-P(DEA-co-CMA)) was synthesized via atom transfer radical polymerization (ATRP). Block copolymer nanogels could be easily prepared by first photo-cross-linking of the micelles at pH > 7 and then adjusting the solution to pH < 7. The photo-cross-linking was proved to be reversibly controlled under alternative irradiation of UV light at 365 nm and 254 nm. As a result, the cross-linking degrees and sizes of the nanogels can be easily controlled by alternatively UV light irradiation. Finally, the nanogels can serve as nanoreactors for the synthesis of gold nanoparticles. The protonated DEA units were first coordinated with HAuCl4, and then the electrostatically bounded AuCl4− anions were reduced to gold nanoparticles by NaBH4. The nanogel-supported gold nanoparticles were used in chemical catalysis. The pH-responsive photo-cross-linked nanogels have been characterized using dynamic light scattering, transmission electron microscopy, UV–vis spectra and 1H NMR spectroscopy measurements, respectively.
Co-reporter:Gongyan Liu;Xiaofen Hu;Chaojian Chen
Journal of Applied Polymer Science 2010 Volume 118( Issue 6) pp:
Publication Date(Web):
DOI:10.1002/app.32758
Abstract
The poly(2-methacryloyloxyethyl phosphorylcholine)-block-poly(D,L-lactide) (PMPC-b-PLA) was specially designed to develop biomimetic giant vesicles (GVs) and giant large compound vesicles via a simple spontaneous assemble in aqueous solution. The weight fraction of the hydrophilic PMPC block (fPC) was proved to play an important role in the size and morphology control of the self-assembled aggregates. The GVs with controlled micrometer size and biomimetic PMPC corona have great potential as artificial cell models. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010
Co-reporter:Li-Ping Lv;Jian-Ping Xu;Xiang-Sheng Liu;Gong-Yan Liu;Xuan Yang
Macromolecular Chemistry and Physics 2010 Volume 211( Issue 21) pp:2292-2300
Publication Date(Web):
DOI:10.1002/macp.201000458
Co-reporter:Liyan Shen, Jinhong Fu, Ke Fu, Catherine Picart, and Jian Ji
Langmuir 2010 Volume 26(Issue 22) pp:16634-16637
Publication Date(Web):September 29, 2010
DOI:10.1021/la102928g
A humido-responsive free-standing film has been created using layer-by-layer assembly technique. Polyethylenimine (PEI) at high pH was assembled with poly(acrylic acid) (PAA) at low pH on a Teflon substrate to yield a micro-nanostructured surface that can be made superhydrophobic after being coated with a low surface energy compound. The resulting asymmetric free-standing film with one surface being superhydrophobic while the other is hydrophilic after detachment from the substrate can undergo reversible bending/unbending shape transitions when the environmental humidity is changed. The bending/unbending movement of the free-standing film can be ascribed to the different responses of these two surfaces to humidity.
Co-reporter:Quankui Lin, Xin Ding, Fuyu Qiu, Xiaoxiao Song, Guosheng Fu, Jian Ji
Biomaterials 2010 31(14) pp: 4017-4025
Publication Date(Web):
DOI:10.1016/j.biomaterials.2010.01.092
Co-reporter:XueFei Wang;KeFeng Ren;QuanKui Lin
Science China Chemistry 2010 Volume 53( Issue 3) pp:508-513
Publication Date(Web):2010 March
DOI:10.1007/s11426-010-0081-4
An efficient and safe gene delivery system remains a challenge in the development of gene therapy. Polycation-based gene nanoparticles are a typical non-viral gene delivery system, which are able to transfect cells in vitro and in vivo. This paper reported a facile method for constructing biodegradable multilayers via layer-by-layer self-assembly, in which the polycation-based gene nanoparticles were loaded. Through this surface-mediated delivery system, adherent cells on the multilayer could be transfected in situ. Gene nanoparticles-loaded multilayers transfect cells with higher efficiency than naked DNA-loaded multilayers because of the complex configuration of the DNA. DNA nanoparticles/PGA multilayers constructed on the scaffold surface could also realize in situ transfection on the adherent cells. The well-structured, easy-processed multilayers may provide a novel approach to precisely controlled delivery of gene nanoparticles, which may have potential applications for gene therapy in tissue engineering and medical implants.
Co-reporter:Qiao Jin;Gongyan Liu
Journal of Polymer Science Part A: Polymer Chemistry 2010 Volume 48( Issue 13) pp:2855-2861
Publication Date(Web):
DOI:10.1002/pola.24062
Abstract
A novel photo and thermo double-responsive block copolymer was developed to fabricate micelles and reverse micelles in aqueous solution. The block copolymer was synthesized by ATRP block copolymerization of a spiropyran- containing methacrylate (SPMA) with di(ethylene glycol) methyl ether methacrylate (DEGMMA). By facile control of the photo irradiation and solution temperature, PSPMA-core and PDEGMMA-core micelles can be obtained, respectively. The thermo- and photo-responsive micelles were used as smart polymeric nanocarriers for controlled encapsulation, triggered release, and re-encapsulation of model drug coumarin 102. The double-responsive self-assembly and disassembly were tracked by dynamic light scattering, transmission electron microscopy, and fluorescence spectroscopy. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 2855–2861, 2010
Co-reporter:Qiao Jin, Xiangsheng Liu, Gongyan Liu, Jian Ji
Polymer 2010 Volume 51(Issue 6) pp:1311-1319
Publication Date(Web):11 March 2010
DOI:10.1016/j.polymer.2010.01.026
Poly(butanedioic acid, 1-[3-[(2-methyl-1-oxo-2-propen-1-yl)oxy]propyl] ester)-b-poly(methoxydi(ethylene glycol) methacrylate-co-4-methyl-[7-(methacryloyl)oxyethyloxy] coumarin) (PSPMA-b-P(DEGMMA-co-CMA)) block copolymer was synthesized via atom transfer radical polymerization (ATRP). The temperature and pH responsive micellization behaviors of PSPMA-b-P(DEGMMA-co-CMA) were investigated to obtain P(DEGMMA-co-CMA)-core and PSPMA-core micelles. After the two types of micelles were exposed to 365 nm UV light, core cross-linked (CCL) micelles and shell cross-linked (SCL) micelles were facilely prepared. The photo cross-linking was proved to be reversibly controlled under alternative irradiation of 365 nm and 254 nm UV light. More interestingly, block copolymer nanogels were fabricated by translating the hydrophobic core of the CCL and SCL micelles into hydrophilic via adjusting the temperature and pH. The sizes of the block copolymer nanogels can be facilely controlled by UV light irradiation. The introduction of reversibly photo cross-linkable groups into the double responsive block copolymers provides a novel approach to develop more sophisticated, controllable, and smarter nanocarriers that might have great potentials in biomedical applications.
Co-reporter:Qiao Jin, Li-Ping Lv, Gong-Yan Liu, Jian-Ping Xu, Jian Ji
Polymer 2010 Volume 51(Issue 14) pp:3068-3074
Publication Date(Web):24 June 2010
DOI:10.1016/j.polymer.2010.04.061
Phenylboronic acid-containing thermo-responsive block copolymer, poly(ethylene oxide)-b-poly(methoxydi(ethylene glycol) methacrylate-co- aminophenylboronic acid ethyl methacrylate) (PEO-b-P(DEGMMA-co-PBAMA)), was employed to investigate the multiple micellization and dissociation transitions. The unique sugar- and pH-responsive properties of phenylboronic acid were interesting to provide two parallel approaches to tune the critical micellization temperature (CMT) and multiple micellization of thermo-responsive block copolymer. The block copolymers were molecularly soluble below 21 °C and underwent micellization above 21 °C at pH 8.7. After glucose was added at 24 °C, hydrophobic phenylboronic acid was changed to hydrophilic boronate–glucose complex and the CMT of the thermo-sensitive block was increased which caused the dissociation of micelles. In parallel, if the solution pH was increased from 8.7 to 11 at 25 °C, micelles were disrupted because of the formation of hydrophilic phenylboronate anion, which elevated the CMT of the thermo-sensitive block polymer. The introduction of phenylboronic acid groups into the thermo-responsive block copolymers provides a novel approach to tune the multiple micellization and dissociation transitions that might have great potentials in biomedical applications.
Co-reporter:Wei Sun, Zhen Shao, Jian Ji
Polymer 2010 Volume 51(Issue 18) pp:4169-4175
Publication Date(Web):19 August 2010
DOI:10.1016/j.polymer.2010.07.008
Particle-assisted fabrication of honeycomb-structured hybrid films was carried out by employing particles as stabilizers in the breath figures (BF) method. Such a procedure tested the possibility of the combination of Pickering emulsions and breath figures, which are two classical self-assembly processes. Regularly patterned porous polystyrene film with particles decorating the inside walls of the open pores can be readily prepared. Silica particles were used as a model candidate to study the influence of both physical and chemical factors, including size, wettability, and application quantity, of the particles on BF pattern formation. Different assembling characteristics of the particles under different circumstances are also discussed. To further extend the application of such particle-assisted, bottom-up surface patterning technique to other kinds of particles, polystyrene particles and poly(N-isopropylacrylamide)-co-acrylic acid microgels were employed to serve as stabilizers in BF method. As expected, all three kinds of particles, including solid inorganic, solid polymeric and microgel ones, succeeded in assisting in the formation of BF arrays in polymer films. The introduction of Pickering-emulsion effect into BF method can provide new possibilities to develop particle-functionalized porous surface.
Co-reporter:Weiyong Yuan, Jinhong Fu, Kai Su, Jian Ji
Colloids and Surfaces B: Biointerfaces 2010 Volume 76(Issue 2) pp:549-555
Publication Date(Web):1 April 2010
DOI:10.1016/j.colsurfb.2009.12.017
Chitosan and heparin multilayer films were successfully constructed via layer-by-layer self assembly. These films were used as a polymeric template to synthesize silver nanoparticles. The silver concentration and nanoparticle size can be simply controlled by the assembly pH and loading pH, as demonstrated by UV–visible spectroscopy, transmission electron microscopy and atomic absorbance spectroscopy. The pH tunable uncompensated charge density within the multilayer films is believed to have great effect on the loading of silver ions, and then control the size and amount of silver nanoparticles within multilayer films. The antibacterial experiment shows that the silver nanoparticle-loaded chitosan/heparin multilayer films exhibit greatly enhanced antibacterial performance compared to the chitosan/heparin multilayer films without silver nanoparticles. In addition, the strong antibacterial property of silver nanoparticle-loaded films can last more than 1 month. Our method of in situ synthesis of metal nanoparticles in biocompatible multilayer films might provide great potential to design biofunctional nanocomposite films.
Co-reporter:Xiaofen Hu and Jian Ji
Langmuir 2010 Volume 26(Issue 4) pp:2624-2629
Publication Date(Web):September 18, 2009
DOI:10.1021/la902719k
Layer-by-layer assembly has shown a great deal of promise in biomedical coatings, as well as local drug delivery systems. The poor loading capacity of hydrophobic drugs within the multilayers is a drawback in their potential applications. Herein, sulfonated hyperbranched polyether (HBPO−SO3) with a hydrophobic core was incorporated into LBL films to provide nanoreservoirs for hydrophobic guest molecules. HBPO−SO3 was proven to form stable micelles in the sodium acetate and acetic acid buffer solution (HAc buffer) for LbL assembly. The QCM and ellipsometry experiments demonstrated that the LBL films can be fabricated via alternating deposition of HBPO−SO3 micelles and chitosan. The fluorescence emission spectra verified that the hydrophobic pyrene can be incorporated both by pre-encapsulation in HBPO−SO3 micelles and post-diffusion in preassembled multilayer films. Compared with the pre-encapsulation approach, the post-diffusion process was more efficient in incorporating hydrophobic guest molecules into the LbL films and carried out a much more controllable release of the guest molecules. A multifunctional coating with potential anticoagulation, antibacterial, and local release of hydrophobic drug Probucal, which has powerful antioxidant properties and can prevent restenosis after coronary angioplasty, was then developed via post-diffusion of the anti-restenosis agents into the multilayer films of HBPO−SO3 and chitosan.
Co-reporter:Jian-Ping Xu, Xi Yang, Li-Ping Lv, Yu Wei, Fang-Min Xu, and Jian Ji
Langmuir 2010 Volume 26(Issue 22) pp:16841-16847
Publication Date(Web):October 13, 2010
DOI:10.1021/la102929k
Nanocomposites constructed from metallic nanoparticles and amphiphilic copolymers have attracted substantial interest for various potential applications. Here we report on the nanocomposites prepared through cross-linking pluronic micelles with gold nanoparticles. The covalent binding of gold nanoparticles onto the micelles and the thermoresponsibility of the system was followed via ultraviolet−visible spectroscopy, dynamic light scattering, transmission electron microscopy, and fluorescence spectroscopy. The gold-nanoparticle-stabilized pluronic micelles can take thiol-exchange reaction with glutathione and their morphology spontaneously evolved and reassembled into large “vesicular”-like nanocapsules. Obvious temperature responsibility was followed in the gold-nanoparticle-stabilized pluronic micelles system and also the glutathione triggered nanocapsules systems. It is believed that the high stability and glutathione responsibility of the Au-NPs shell-cross-linked micelles allowed for high potential in drug delivery and biosensors.
Co-reporter:Wei Sun, Liyan Shen, Jiaming Wang, Ke Fu and Jian Ji
Langmuir 2010 Volume 26(Issue 17) pp:14236-14240
Publication Date(Web):August 4, 2010
DOI:10.1021/la102136r
The pH-amplified exponential growth layer-by-layer (LBL) self-assembly process was directly performed on honeycomb-patterned substrate for achievement of “guided patterning” of polyelectrolyte multilayers. Polyethylenimine (PEI) and poly(acrylic acid) (PAA) were used as polyanions, and their pH were carefully tuned to achieve pH-enhanced exponential growth. Guided by underlying hexagonally patterned islandlike poly(dimethylsiloxane) (PDMS) arrays, the diffusive polyelectrolytes rapidly interweaved into linear, multilayered structures distributed along the grooves between the patterned protuberate and formed a regular network of multilayered film with uniform mesh size. Netlike “knitting” of polyelectrolyte multilayers on honeycomb-patterned substrate has been realized by following this procedure. Superhydrophobic surfaces could be readily obtained after several bilayers of LBL assembly (with thermal cross-linking and surface fluorination by chemical vapor deposition), indicating that successful fabrication of functional micro- and nanoscale hierarchical structures can be achieved. Both high- and low-adhesion superhydrophobic surfaces (“petal effect” and “lotus effect”) can be obtained with different bilayers of assembly, proving that different levels of nano- to microstructural hierarchy can be realized using this method. Furthermore, we were able to get topographically asymmetric, free-standing, polyelectrolyte multilayer films in the case that we performed more than eight bilayers of assembly. This research reported template-directed LBL patterning assembly for the first time. It provides a beneficial exploration for the surface patterning technique for the LBL assembly process.
Co-reporter:Leize Zhu;Qiao Jin;Jianping Xu;Jiacong Shen
Journal of Applied Polymer Science 2009 Volume 113( Issue 1) pp:351-357
Publication Date(Web):
DOI:10.1002/app.29750
Abstract
Water-soluble multi-walled carbon nanotubes (MWNTs) were prepared via surface-initiated atom transfer radical polymerization (ATRP) of 2-(methacryloyloxy) ethyl phosphorylcholine (MPC) from carbon nanotubes (CNTs). The success of the surface functionalization of MWNTs with poly(2-(methacryloyloxy) ethyl phosphorylcholine) (pMPC) was ascertained using fourier transform infrared spectrophotometry (FTIR), thermogravimetric analysis (TGA), hydrogen nuclear magnetic resonance (1H-NMR), and transmission electron microscopy (TEM). Different from the results of the previous work, in our work, we demonstrate that the amount of pMPC on CNTs can be easily regulated by ATRP approach. In addition, from TGA results, a linear relationship between the weight loss fraction of MWNT-pMPC and the weight of MPC fed and as high as 48.1% weight loss of MWNT-pMPC (MWNTs grafted by pMPC) are observed. Through TEM, the core-shell structure of MWNT-pMPC is clearly observed, which is also different from the previous report. The pMPC-modified MWNTs are highly soluble, which can also resist pH and saline concentration changes and remain stable in physiological environment. PMPC-modified MWNT does not significantly affect the blood coagulation as demonstrated in plasma recalcification time (PRT) test. These highly soluble MWNTs are expected to enable their wide use in biomedical areas. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Co-reporter:Quan-Kui Lin, Ke-Feng Ren, Jian Ji
Colloids and Surfaces B: Biointerfaces 2009 Volume 74(Issue 1) pp:298-303
Publication Date(Web):1 November 2009
DOI:10.1016/j.colsurfb.2009.07.036
Sustained release of DNA from the surface of materials represents a promising approach to combine the gene therapy and implantable biomaterials. The nonviral chitosan-DNA complexes were incorporated into the multilayer via layer-by-layer deposition with hyaluronic acid (HA). The UV–vis spectroscopy and atomic force microscopy (AFM) results showed the successful construction of the nonviral complex contained multilayers. The complexes were releasable in physiological condition and a sustained release manner was gained when the multilayer was crosslinked. The cell viability test and the gene transfection assay showed that the natural polyelectrolyte-based nonviral complex incorporated multilayer not only had good cytocompatibility, but also possessed the in vitro gene transfection ability. This kind of surface-mediated nonviral complex incorporated multilayer may have great potential in the localized and controlled delivery of DNA in biomedical implants and tissue engineering application.
Co-reporter:Qingshan Wei;Wenbo Zhou;Jiacong Shen
Nanoscale Research Letters 2009 Volume 4( Issue 1) pp:
Publication Date(Web):2009 January
DOI:10.1007/s11671-008-9206-5
Thermosensitive nanocables consisting of Au nanowire cores and poly(N-isopropylacrylamide) sheaths (denoted as Au/PNIPAAm) were synthesized by surface-initiated atom transfer radical polymerization (SI-ATRP). The formation of PNIPAAm sheath was verified by Fourier transform infrared (FTIR) and hydrogen nuclear magnetic resonance (1H NMR) spectroscopy. Transmission electron microscope (TEM) results confirmed the core/shell structure of nanohybrids. The thickness and density of PNIPAAm sheaths can be adjusted by controlling the amount of cross-linker during the polymerization. Signature temperature response was observed from Au/cross-linked-PNIPAAm nanocables. Such smart nanocables show immense potentials as building blocks for novel thermosensitive nanodevices in future.
Co-reporter:Qiao Jin;XiangSheng Liu;JianPing Xu
Science China Chemistry 2009 Volume 52( Issue 1) pp:64-68
Publication Date(Web):2009 January
DOI:10.1007/s11426-008-0106-4
The water-soluble Ag nanoparticles capped with novel zwitterionic thioalkylated phosphorylcholine were synthesized. The Ag nanoparticles showed remarkable stability in saline media with salt concentrations as high as 2.0 mol/L and plasma using UV-vis absorption spectroscopy. Similarly, compared with tiopronin and citrate-protected Ag nanoparticles, the zwitterionic phosphorylcholine Ag nanoparticles did not precipitate out of solution when charged polyelectrolytes or biopolymers were added. The zwitterionic phosphorylcholine might be a better ligand for stabilizing metal nanoparticles.
Co-reporter:Jian-Ping Xu, Fei-Fan Li, Jian Ji, Jia-Cong Shen
Thin Solid Films 2009 Volume 517(Issue 13) pp:3681-3685
Publication Date(Web):1 May 2009
DOI:10.1016/j.tsf.2009.02.120
A tunable and green enzyme biocatalyst route to develop superhydrophobic surfaces on microstructured poly(ethylene terephthalate) (PET) films by the tailoring of the micro- and nano scale hierarchical structures is described. Upon the aminolysis of PET films with hexamethylenediamine, the primary amine groups are covalently attached onto the PET surfaces and microstructured pattern is formed. The binding of citrate-stabilized Au nanoparticles onto the PET surfaces via the covalent bond between the gold nanoparticles and the primary amine groups introduced on the PET surfaces was followed spectroscopically. The biocatalytic enlargement of the Au nanoparticles using the enzyme-generated H2O2 as reducing agent for the reduction of AuCl4− at the attached Au nanoparticle seeds on the PET surfaces was followed by spectroscopic means and atom force microscopy (AFM). The AFM experiments indicated that micro- and nano scale hierarchical structures were tailored by the enzyme biocatalyst route. Superhydrophobic surfaces with water contact angles as high as 158.6 ± 2.0° was achieved upon the chemisorption of 1-octadecanethiol as low surface energy material. This route can be potentially applicable to superhydrophobic PET-based microfluidic devices with reduced friction surfaces.
Co-reporter:Jinhong Fu, Jian Ji, Liyan Shen, Alexander Küller, Axel Rosenhahn, Jiacong Shen and Michael Grunze
Langmuir 2009 Volume 25(Issue 2) pp:672-675
Publication Date(Web):December 16, 2008
DOI:10.1021/la803692v
We report a direct method to amplify the exponential growth of multilayers significantly by the alternating deposition of polyethylenimine (PEI) at high pH and poly(acrylic acid) (PAA) at low pH. The alternating pH switches the degree of ionization of the polyelectrolytes in the multilayers, which enhances the diffusion of PEI into and out of the film and hence increases the deposited mass per cycle. The synergetic action of the pH-tunable charge density and diffusivity of the weak polyelectrolytes provides a new method for the enhanced growth of multilayers with hierarchal micro- and nanostructured surfaces.
Co-reporter:Xuefei Wang and Jian Ji
Langmuir 2009 Volume 25(Issue 19) pp:11664-11671
Publication Date(Web):September 8, 2009
DOI:10.1021/la9013575
The multilayers of poly(l-lysine) (PLL) and hyaluronic acid (HA) were constructed by alternating deposition of PLL at high pH and HA at low pH. The exponential growth of the multilayer was proved to be amplified by increasing the pH difference between the two deposition solutions. The exponential growth multilayers of PLL/HA assembled at different pH were utilized as reservoirs for loading a trans-activating transcriptional factor (TAT) peptide. The confocal laser scanning microscopy (CLSM) results indicated that the FITC-labeled TAT could diffuse throughout the exponentially growing PLL/HA film. The amount of peptide embedded within multilayer could be adjusted by both multilayer assembly pH and the TAT loading pH. Compared with (PLL/HA 6.5/6.5)5 multilayer (PLL/HA a/b means that the multilayer film was constructed by using PLL at pH a and HA at pH b), the (PLL/HA 9.5/2.9)5 film can be loaded with more TAT peptide at the same loading pH 6.5. The excess of positively charged TAT peptide within (PLL/HA 9.5/2.9)5 film could not only be ascribed to its extraordinary thickness but also be attributed to its uncompensated negative charge density enhanced by the pH difference between film buildup and peptide loading process. Increasing of the TAT loading pH from 6.5 to 9.5, which increases the pH difference between multilayer assembly and peptide loading process, enhances the uncompensated charge density within (PLL/HA 9.5/2.9)5 film and elevates the peptide density from 13.8 to 25.0 μg/cm2. Compared with direct layer-by-layer assembly of TAT and HA, the postdiffusion of TAT into (PLL/HA 9.5/2.9)5 film was loaded much more peptide. The postdiffusion of peptide into a rapid growth multilayer can be more favorable to load and sustainedly release functional oligo-peptide. The cell culture results indicated that the TAT embedded within the film maintained the ability to traverse across the Hep G2 cell membrane. The functionalized (PLL/HA 9.5/2.9)5 TAT 9.5 film was more efficient than the equivalent amount of free TAT peptide in the TAT uptake test. The postdiffusion of oligo-peptide within an exponential growth multilayer can serve as an effective approach for localized and sustained peptide delivery.
Co-reporter:Qiao Jin, Jian-Ping Xu, Jian Ji and Jia-Cong Shen
Chemical Communications 2008 (Issue 26) pp:3058-3060
Publication Date(Web):22 Apr 2008
DOI:10.1039/B801959B
Zwitterionic
phosphorylcholine showed better stabilization than oligo(ethylene glycol) in protecting big gold nanoparticles.
Co-reporter:Qingshan Wei;Jiacong Shen
Macromolecular Rapid Communications 2008 Volume 29( Issue 8) pp:645-650
Publication Date(Web):
DOI:10.1002/marc.200800009
Co-reporter:Jian-Ping Xu, Xiao-Li Wang, De-Zeng Fan, Jian Ji, Jia-Cong Shen
Applied Surface Science 2008 Volume 255(Issue 2) pp:538-540
Publication Date(Web):15 November 2008
DOI:10.1016/j.apsusc.2008.06.098
Abstract
The biomimetic phospholipid anti-biofouling multilayers were constructed on the biomedical poly(ethylene terephthalate) (PET) through the combination of layer-by-layer assembly and Michael addition reaction. Two biomacromolecules with opposite charges, alginate and chitosan, were sequentially adsorbed onto PET samples. The assembled multilayer was subsequently crosslinked with glutaraldehyde and biomimetic phospholipids was introduced into the assembled multilayer through the Michael addition of 2-methacryloyloxyethyl phosphorylcholine (MPC). The multilayer and phospholipid-modified PETs showed excellent hemocompatibility.
Co-reporter:Weiyong Yuan;Jinhong Fu;Jiacong Shen
Journal of Biomedical Materials Research Part B: Applied Biomaterials 2008 Volume 85B( Issue 2) pp:556-563
Publication Date(Web):
DOI:10.1002/jbm.b.30979
Abstract
A multifunctional multilayered film containing TiO2 nanoparticles as contact-active antibacterial agent and nanosilver as a release-active antibacterial agent was fabricated via layer-by-layer assembly. TiO2 nanoparticles with the anatase crystalline dominant structure were synthesized via a sol-gel method. The QCM, AFM, and contact angle measurement results indicated that the TiO2 nanoparticle-chitosan was successfully assembled with heparin via layer-by-layer assembly. The UV visible spectroscopy demonstrated that the silver ions could be loaded into the multilayers and in situ synthesize silver nanoparticles in the multilayers template. The short-term antibacterial assay showed the TiO2-chitosan/heparin multilayers loaded with nanosilver was bactericidal both in the low intensity UV light and in the dark. The long-term antibacterial assay indicated although the antibacterial in dark decreased with the PBS immersion time, the hybrid multilayered films sustained the long-term antibacterial in the low intensity UV light. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2008
Co-reporter:Wei Sun, Jian Ji and Jiacong Shen
Langmuir 2008 Volume 24(Issue 20) pp:11338-11341
Publication Date(Web):September 19, 2008
DOI:10.1021/la8024217
The self-assembly of nanoparticles at the fluid/fluid interface (Pickering emulsions) in the breath figures (BF) method have been explored to direct nanoparticles onto BF microarrays and adjust the BF assembly in microsize. Circular rings of nanoparticle-decorated honeycomb-structured polymeric film can be obtained by a one-step process. The combination of Pickering emulsions and capillary flow in the BF method may be responsible for the formation of this intriguing structure.
Co-reporter:Liyan Shen, Jian Ji and Jiacong Shen
Langmuir 2008 Volume 24(Issue 18) pp:9962-9965
Publication Date(Web):August 22, 2008
DOI:10.1021/la801774v
Superhydrophobic surfaces with high reflectivity might provide a promising self-cleaning approach in a wide variety of optical applications ranging from traffic to solar energy industries. However, the contradiction between the hierarchical micronanostructure and the high reflectivity is a challenge for superhydrophobic materials with high reflectivity. Here we report a facile method to fabricate a superhydrophobic silver film with reflectivity as high as that of polished silicon by carefully controlling the seed-induced silver mirror reaction.
Co-reporter:J. Fu;J. Ji;J. Shen
Advanced Materials 2007 Volume 19(Issue 18) pp:
Publication Date(Web):10 SEP 2007
DOI:10.1002/adma.200790070
Co-reporter:J. Fu;J. Shen;J. Ji
Advanced Materials 2007 Volume 19(Issue 13) pp:
Publication Date(Web):26 JUN 2007
DOI:10.1002/adma.200790046
Co-reporter:Xiaolin Li;Xiaoli Wang;Jiacong Shen;Youxiang Wang
Macromolecular Rapid Communications 2007 Volume 28(Issue 5) pp:660-665
Publication Date(Web):12 MAR 2007
DOI:10.1002/marc.200600723
A novel comb-like derivative CPEG-g-cholesterol was prepared by the reaction of cholesteryl chloroformate with hydroxyl groups of CPEG. The TEM and SEM results showed that CPEG-cholesterol spontaneously aggregated vesicles with the membrane thickness of 4.27 ± 0.48 nm. Compared with the vesicles formed by comb-like PEG (CPEG), the derivation of cholesteryl chloroformate increased the thickness of vesicle membrane and developed corrugations. The hydrophobic doxorubicin (Dox) was added into the solution of CPEG and CPEG-g-cholesterol to test their vesicle stability. The drug-loaded vesicles of CPEG-g-cholesterol still existed but those of CPEG disappeared, which indicated that stability of vesicles was enhanced by the derived cholesteryl chloroformate. The vesicles were further cross-linked by the reaction between divinyl sulfone (DVS) and the hydroxy groups in the side chains of the CPEG and CPEG-g-cholesterol. Both cross-linked vesicles of CPEG and CPEG-g-cholesterol entrapped considerable hydrophobic Dox in the vesicles membrane. The spontaneous vesicles of CPEG-g-cholesterol and the crosslinked vesicles of CPEG and CPEG-g-cholesterol might have great potential as a cargo of the hydrophobic drug.
Co-reporter:QingShan Wei;JinHong Fu;JiaCong Shen
Science China Chemistry 2007 Volume 50( Issue 3) pp:418-424
Publication Date(Web):2007 June
DOI:10.1007/s11426-007-0028-6
The synthesis of norvancomycin (NVan)-capped silver nanoparticles (Ag@NVan) and their notable in vitro antibacterial activities against E. coli, a Gram-negative bacterial strain (GNB), are reported here. Mercaptoacetic acid-stabilized spherical silver nanoparticles with a diameter of 16±4 nm are prepared by a simple chemical reaction. The formation process of the silver nanoparticles is investigated by UV-visible (UV-vis) spectroscopy and transmission electron microscopy (TEM). NVan is then grafted to the terminal carboxyl of the mercaptoacetic acid in the presence of N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDAC). The TEM images of single bacteria treated with Ag@NVan show that plenty of Ag@NVan aggregate in the cell wall of E. coli. A possible antibacterial mechanism is proposed that silver nanoparticles may help destroy the stability of the outer membrane of E. coli, which makes NVan easier to bind to the nether part of the peptidoglycan structure. The antibacterial activities of silver nanoparticles on their own, together with the rigid polyvalent interaction between Ag@NVan and cell wall, enables Ag@NVan to be an effective inhibitor of GNB. This kind of bionanocomposites might be used as novel bactericidal materials and we also provide an effective synthesis method for preparing functional bioconjugated nanoparticles here.
Co-reporter:J. Ji;J. Fu;J. Shen
Advanced Materials 2006 Volume 18(Issue 11) pp:1441-1444
Publication Date(Web):26 APR 2006
DOI:10.1002/adma.200502453
Hierarchical micro- and nanostructures can be produced simultaneously by the novel layer-by-layer assembly described here. The multilayer films, grown by an exponential growth mechanism that can be amplified by adding silver ions, showed extreme hydrophobicity and a lotus-leaf-like amplification of the surface roughness. The figure clearly demonstrates the superhydrophobic nature of the multilayer film.
Co-reporter:Xiaolin Li;Jiacong Shen
Macromolecular Rapid Communications 2006 Volume 27(Issue 3) pp:214-218
Publication Date(Web):23 JAN 2006
DOI:10.1002/marc.200500685
Summary: A novel comb-like poly(ethylene glycol) (CPEG), with dominant water-soluble PEG, is found to spontaneously aggregate into vesicles above a certain concentration in water. The hollow, three-dimensional structure of the vesicles is proven by TEM, SEM, and AFM. The diameters of the vesicles are from 200 to 500 nm with 50 nm walls. The spontaneously formed vesicles can be further cross-linked by the reaction between divinyl sulfone (DVS) and the hydroxy groups in the side chains of the CPEG. The spontaneously formed vesicles with dense reactive hydroxy groups will have great potential in both applications and research.
Co-reporter:Jian Ji;Dezeng Fan;Jiacong Shen;Jinhong Fu
Journal of Biomedical Materials Research Part A 2006 Volume 79A(Issue 3) pp:665-674
Publication Date(Web):10 JUL 2006
DOI:10.1002/jbm.a.30819
Antibacterial multilayer films containing nanosilver were prepared via layer-by-layer fashion. PET film was aminolyzed with 1,6-hexanediamine to introduce amino groups on PET film surface; chitosan–silver nitrate complex and heparin were alternately deposited onto an aminolyzed PET film surface, and subsequently, the silver ions within the multilayer films were reduced with ascorbic acid to form silver nanoparticles. UV–visible spectroscopy and transmission electron microscopy confirmed the formation of well-dispersed nanosilver particles with sizes (10–40 nm) that depended on the initial concentration of silver ions in chitosan solution and the pH of ascorbic acid solution. The chitosan/heparin multilayer films were possessed of bactericidal effect on Escherichia coli (E. coli), and this antibacterial effect could be significantly enhanced by the incorporation of silver nanoparticles into the multilayer films. The multilayer films containing nanosilver were not only effective as antibacterial but also as anticoagulant coating. And cell toxicity evaluation suggested that the multilayer films containing nanosilver did not show any cytotoxicity. The multilayer films containing nanosilver may have good potentials for surface modification of medical devices, especially for cardiovascular implants. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Co-reporter:Kefeng Ren;Jiacong Shen
Macromolecular Rapid Communications 2005 Volume 26(Issue 20) pp:1633-1638
Publication Date(Web):6 OCT 2005
DOI:10.1002/marc.200500482
Summary: The multilayers of polycation-based non-viral DNA nanoparticles and biodegradable poly(L-glutamic acid) (PGA) were constructed by a layer-by-layer (LbL) technique. Poly(ethyleneimine) (PEI) was used to condense DNA to develop non-viral DNA nanoparticles. AFM, UV-visible spectrometry, and TEM measurements revealed that the PEI-DNA nanoparticles were successfully incorporated into the multilayers. The well-structured, easily processed multilayers with the non-viral DNA nanoparticles may provide a novel approach to precisely control the delivery of DNA, which may have great potential for gene therapy applications in tissue engineering, medical implants, etc.
Co-reporter:He Zhang, Ke-feng Ren, Hao Chang, Jin-lei Wang, Jian Ji
Biomaterials (February 2017) Volume 116() pp:95-105
Publication Date(Web):February 2017
DOI:10.1016/j.biomaterials.2016.11.042
Co-reporter:Yin Wang, Dandan Li, Haibo Wang, Yangjun Chen, Haijie Han, Qiao Jin and Jian Ji
Chemical Communications 2014 - vol. 50(Issue 66) pp:NaN9392-9392
Publication Date(Web):2014/07/09
DOI:10.1039/C4CC03978E
The first attempt of constructing pH responsive supramolecular prodrug micelles based on cucurbit[8]uril is reported. The obtained prodrug micelles are found to be able to inhibit proliferation of cancer cells. It is anticipated that this facile strategy may open a novel avenue for the development of multifunctional drug delivery systems.
Co-reporter:Li-mei Wang, Hao Chang, He Zhang, Ke-feng Ren, Huan Li, Mi Hu, Bo-chao Li, M. Cristina L. Martins, Mário A. Barbosa and Jian Ji
Journal of Materials Chemistry A 2015 - vol. 3(Issue 38) pp:NaN7553-7553
Publication Date(Web):2015/08/19
DOI:10.1039/C5TB01151E
The stiffness of the substrates has been found to have a strong effect on cell behaviors, especially on cell adhesion, which is the first cellular event when cells contact materials. Much effort has been made to develop the materials with controlled stiffness for regulating cell adhesion. However, most available strategies for controlling the stiffness of material surfaces are generally limited to be static, which means that the stiffness is fixed during cell adhesion. Herein, we developed polyelectrolyte multilayer films (PEMs), and their stiffness can be dynamically modulated by mild stimuli. The PEMs were made by alternative deposition of poly-L-lysine (PLL) and thiol group modified hyaluronan (HA-SH) using the layer-by-layer assembly technique. The (PLL/HA-SH) multilayers can be cross-linked via oxidation of thiol groups. After crosslinking, the stiffness was increased and the adhesion of fibroblast cells was promoted. The stiffness of the multilayer films can be down-regulated dynamically by adding glutathione (GSH) in the medium, leading to in situ reduction of cell adhesion. Our study provides a promising strategy for the development of material surfaces with dynamically changeable stiffness, which is of great potential in the field of cell-based biomaterials.
Co-reporter:Qiao Jin, Jian-Ping Xu, Jian Ji and Jia-Cong Shen
Chemical Communications 2008(Issue 26) pp:NaN3060-3060
Publication Date(Web):2008/04/22
DOI:10.1039/B801959B
Zwitterionic
phosphorylcholine showed better stabilization than oligo(ethylene glycol) in protecting big gold nanoparticles.
Co-reporter:Lan Jia, Jian-Ping Xu, Di Li, Shao-Peng Pang, Yuan Fang, Zhe-Gang Song and Jian Ji
Chemical Communications 2010 - vol. 46(Issue 38) pp:NaN7168-7168
Publication Date(Web):2010/08/18
DOI:10.1039/C0CC01244K
An alkaline phosphatase activity detection system was constructed based on the different quenching effect of the enzyme substrate and product on the β-CD-functionalized CdTe QDs.
Co-reporter:Yin Wang, Jianwei Du, Youxiang Wang, Qiao Jin and Jian Ji
Chemical Communications 2015 - vol. 51(Issue 14) pp:NaN3002-3002
Publication Date(Web):2015/01/19
DOI:10.1039/C4CC09274K
A novel type of dual pH-responsive supramolecular prodrug micelles based on host–guest interactions of water-soluble pillar[5]arene (WP5) and methyl viologen functioned doxorubicin (MV-DOX) was prepared. It was found that the prodrug micelles could be aggregated upon acidic condition, which led to enhanced accumulation and better therapy effect.
Co-reporter:Wenbo Zhou, Jinyan Shao, Qiao Jin, Qingshan Wei, Jianguo Tang and Jian Ji
Chemical Communications 2010 - vol. 46(Issue 9) pp:NaN1481-1481
Publication Date(Web):2010/01/19
DOI:10.1039/B915125G
The conjugation of zwitterionic phosphorylcholine onto gold nanorods leads to enhanced and selective uptake within cancer cells.
Co-reporter:Yin Wang, Haibo Wang, Yangjun Chen, Xiangsheng Liu, Qiao Jin and Jian Ji
Chemical Communications 2013 - vol. 49(Issue 64) pp:NaN7125-7125
Publication Date(Web):2013/07/04
DOI:10.1039/C3CC43687J
For the first time, pseudopolyrotaxane prodrug micelles with high drug content were prepared in water, which could be used for cancer therapy. It is anticipated that this facile strategy may open a novel avenue for the development of multifunctional drug delivery systems.
Co-reporter:Dan-dan Li, Xia-chao Chen, Ke-feng Ren and Jian Ji
Chemical Communications 2015 - vol. 51(Issue 9) pp:NaN1578-1578
Publication Date(Web):2014/10/28
DOI:10.1039/C4CC07899C
A pseudo-polycation was prepared based on the supramolecular cucurbit[8]uril ternary complex. It was then layer-by-layer assembled with poly(acrylic acid) to fabricate a stimuli-responsive film, which exhibited disassembly properties in response to stimuli, providing a supramolecular route for the fabrication of free-standing thin films.
Co-reporter:Jin-lei Wang, Ke-feng Ren, Hao Chang, Shi-miao Zhang, Lie-jiang Jin and Jian Ji
Physical Chemistry Chemical Physics 2014 - vol. 16(Issue 7) pp:
Publication Date(Web):
DOI:10.1039/C3CP54354D
Co-reporter:Gongyan Liu, Quanqing Luo, Haiqi Gao, Yuan Chen, Xing Wei, Hong Dai, Zongcai Zhang and Jian Ji
Biomaterials Science (2013-Present) 2015 - vol. 3(Issue 3) pp:NaN499-499
Publication Date(Web):2014/12/22
DOI:10.1039/C4BM00385C
In cancer therapy, surface engineering of drug delivery systems plays an essential role in their colloidal stability, biocompatibility and prolonged blood circulation. Inspired by the cell membrane consisting of phospholipids and glycolipids, a zwitterionic phosphorylcholine functionalized chitosan oligosaccharide (PC-CSO) was first synthesized to mimic the hydrophilic head groups of those amphipathic lipids. Then hydrophobic stearic acid (SA) similar to lipid fatty acids was grafted onto PC-CSO to form amphiphilic PC-CSO-SA copolymers. Cell membrane-mimetic micelles with a zwitterionic surface and a hydrophobic SA core were prepared by the self-assembly of PC-CSO-SA copolymers, showing excellent stability under extreme conditions including protein containing media, high salt content or a wide pH range. Doxorubicin (DOX) was successfully entrapped into polymeric micelles through the hydrophobic interaction between DOX and SA segments. After fast internalization by cancer cells, sustained drug release from micelles to the cytoplasm and nucleus was achieved. This result suggests that these biomimetic polymeric micelles may be promising drug delivery systems in cancer therapy.
Co-reporter:Hongxin Tong, Yin Wang, Huan Li, Qiao Jin and Jian Ji
Chemical Communications 2016 - vol. 52(Issue 20) pp:NaN3969-3969
Publication Date(Web):2016/02/08
DOI:10.1039/C6CC00450D
Novel 5-aminolevulinic acid (ALA) pseudopolyrotaxane prodrug micelles with dual pH-responsive properties were prepared by the host–guest interaction of α-cyclodextrin (α-CD) and poly(ethylene glycol) (PEG). The micelles exhibited pH dependent cellular uptake and pH-sensitive ALA release, enabling enhanced photodynamic therapy.
Co-reporter:Yin Wang, Huan Li, Qiao Jin and Jian Ji
Chemical Communications 2016 - vol. 52(Issue 3) pp:NaN585-585
Publication Date(Web):2015/10/30
DOI:10.1039/C5CC07195J
A simple method to achieve host–guest assembly of gold nanoparticles triggered by intracellular glutathione was demonstrated. The increased size of nanoparticles not only enhanced their retention time within cancer cells, but also induced apoptosis. This strategy may open an avenue for the development of smart nanocarriers for intracellular diagnosis and therapy.
Co-reporter:Haibo Wang, Xiangsheng Liu, Yin Wang, Yangjun Chen, Qiao Jin and Jian Ji
Journal of Materials Chemistry A 2015 - vol. 3(Issue 16) pp:NaN3305-3305
Publication Date(Web):2015/02/27
DOI:10.1039/C4TB01984A
Ideal drug delivery systems should have prolonged circulation in blood, high accumulation in tumors with fast cellular uptake and burst drug release in cancer cells. Herein, a pH-sensitive small-molecule phospholipid prodrug based on phosphorylcholine (PC) was designed to overcome these challenges. The prodrug was synthesized by conjugating doxorubicin (DOX) to 11-mercaptoundecyl phosphorylcholine via an acid-labile hydrazone linker (UnPC-hyd-DOX). This phospholipid prodrug can self-assemble into core–shell micelles with exact and very high drug loading content (56.2%). Interestingly, the PC prodrug micelles can strongly minimize nonspecific phagocytosis by macrophages. They exhibited better ability to be internalized by cancer cells than that of the PEG prodrug micelles, which indicated that the PC shell facilitated cancer cell internalization. Moreover, in vitro results further demonstrated that DOX of phospholipid prodrug micelles can effectively escape from endo/lysosomes to the cytosol and enter the nucleus. An in vivo study demonstrated that these PC prodrug micelles exhibited much lower cardiotoxicity than free DOX. Importantly, PC prodrug micelles showed significantly slower blood clearance than PEG prodrug micelles and free DOX.
Co-reporter:Xiangsheng Liu, Qiao Jin, Ying Ji and Jian Ji
Journal of Materials Chemistry A 2012 - vol. 22(Issue 5) pp:NaN1927-1927
Publication Date(Web):2011/12/06
DOI:10.1039/C1JM14178C
Gold nanoparticles (AuNPs) with excellent resistance to phagocytic uptake by macrophages are achieved via a facile mixed charged zwitterionic self-assembled monolayers (SAMs) surface modification. A series of AuNPs with good dispersity against high salinity, strong resistance to plasma adsorption, persistent stability in cell culture medium and low cytotoxicity are prepared by surface modification with mixed charged SAMs in relatively wide range ratios of oppositely charged thiols. An in vitro study demonstrates that AuNPs modified by mixed charged SAMs effectively minimize the nonspecific cell uptake by either non-phagocytic HUVEC and HepG2 cells or phagocytic RAW 264.7 cells. When different factors that affect cell uptake including incubation time, nanoparticles concentration and incubation mode were evaluated, all results demonstrated that the resistance to phagocytosis by macrophage RAW 264.7 of the zwitterionic AuNPs is even much better than that of the traditional PEGylated AuNPs. A hemolysis assay with human erythrocytes demonstrates the good blood biocompatibility of the zwitterionic AuNPs. The excellent “stealth” properties of the mixed charged AuNPs promise their further biomedical applications both in vitro and in vivo.
Co-reporter:Gong-Yan Liu, Chao-Jian Chen, Dan-Dan Li, Shan-Shan Wang and Jian Ji
Journal of Materials Chemistry A 2012 - vol. 22(Issue 33) pp:NaN16871-16871
Publication Date(Web):2012/07/18
DOI:10.1039/C2JM00045H
Near-infrared light-sensitive polymeric micelles were prepared for the enhanced intracellular delivery of doxorubicin (DOX). The micelles were prepared from dextran-graft-(2-diazo-1,2-naphthoquinone) (Dex-DNQ) amphiphilic copolymers which were synthesized by modification of hydrophilic dextran with hydrophobic DNQ molecules. The hydrophobic DNQ molecule is an attractive photo-trigger group because its UV/NIR-induced Wolff rearrangement can result in a drastic change into a hydrophilic 3-indenecarboxylic acid (3-IC) molecule with pKa of 4.5. Thus, under UV or NIR irradiation, Dex-DNQ micelles will rapidly release encapsulated drugs due to the micelle dissociation. DOX was chosen as an anticancer drug to be encapsulated into the Dex-DNQ micelle with the loading efficiency and content of 60% and 24%, respectively. In vitro cell viability studies, the micelles exhibited higher intracellular DOX release under NIR irradiation at 808 nm, which resulted in significant growth inhibition of HepG2 cancer cells. Fluorescence microscopy and flow cytometry further proved the enhanced intracellular drug release behaviour of DOX-loaded Dex-DNQ micelles under NIR irradiation. We are convinced that this smart drug nanocarrier is potentially useful for cancer chemotherapy.
Co-reporter:Hao Chang, He Zhang, Mi Hu, Xia-chao Chen, Ke-feng Ren, Jin-lei Wang and Jian Ji
Biomaterials Science (2013-Present) 2015 - vol. 3(Issue 2) pp:NaN360-360
Publication Date(Web):2014/12/08
DOI:10.1039/C4BM00321G
In-stent restenosis and thrombosis are the main severe problems that occur after the percutaneous vascular intervention. The competition between endothelial cells (ECs) and smooth muscle cells (SMCs) plays a key role during these pathological changes. The regulation of this competition offers new opportunities to design biomaterials in the cardiovascular fields. Bioactive molecules have been typically employed to increase EC adhesion and thereafter to enhance EC competitiveness; however, this method is associated with limitations from the point of view of practical and industrial applications. Herein, we present an approach to enhance EC competitiveness over that of SMC through the selective EC adhesion, which is achieved by modulating a complex surface stiffness based on the technique of layer-by-layer (LbL) assembly. This complex stiffness can be achieved by regulating the thickness of multilayer films coordinating with a rigid underlying substrate. The selective cell adhesion is attributed to changes in the complex surface stiffness and a different intrinsic property between ECs and SMCs. This study provides a facile and broadly applicable approach for the purpose of the enhancement of EC competitiveness over that of SMC, which has great potential for the development of cell-based functional biomaterials in the cardiovascular field.
Co-reporter:Wenbo Zhou;Xiangsheng Liu
Journal of Materials Chemistry A 2012 - vol. 22(Issue 28) pp:
Publication Date(Web):2012/06/26
DOI:10.1039/C2JM16713A
Dual functionalization of gold nanorods (GNRs) with two kinds of surface ligands has been achieved. Phosphorylcholine (PC) could impart the GNRs with both biostability in the physiological environment and targetability towards cancer cells uniquely. On the other hand, the protein transduction domain of human immunodeficiency virus type 1 Tat peptide could induce the GNRs to be quickly internalized through cell membranes. The inductively coupled plasma mass spectroscopy (ICP-MS), TEM and UV-Vis assays all demonstrated that such dual-ligand GNRs exhibited both fast and selective cancer cell uptake advantages, which were utilized for more efficient cancer cell ablation under near-infrared (NIR) irradiation. This mode of the multivalent scaffold offers an optimized choice for future cell-based therapies.
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![Pentanoic acid, 5-amino-4-[2-(2-mercaptoacetyl)hydrazinylidene]-](/data/chemimg/3781500/2077965-65-0.png)
![Pentanoic acid, 5-amino-4-[2-(2-mercaptoacetyl)hydrazinylidene]-](/data/chemimg/3781500/2077965-65-0_b.png)
![L-Proline,N-[[(2S,3S)-3-[(propylamino)carbonyl]-2-oxiranyl]carbonyl]-L-isoleucyl-](http://img.cochemist.com/ccimg/134500/134448-10-5.png)
![L-Proline,N-[[(2S,3S)-3-[(propylamino)carbonyl]-2-oxiranyl]carbonyl]-L-isoleucyl-](http://img.cochemist.com/ccimg/134500/134448-10-5_b.png)
![Tungstate(3-),tetracosa-m-oxododecaoxo[m12-[phosphato(3-)-kO:kO:kO:kO':kO':kO':kO'':kO'':kO'':kO''':kO''':kO''']]dodeca-,hydrogen (1:3)](http://img.cochemist.com/ccimg/1400/1343-93-7.png)
![Tungstate(3-),tetracosa-m-oxododecaoxo[m12-[phosphato(3-)-kO:kO:kO:kO':kO':kO':kO'':kO'':kO'':kO''':kO''':kO''']]dodeca-,hydrogen (1:3)](http://img.cochemist.com/ccimg/1400/1343-93-7_b.png)
![Acetic acid, 2-[4-(1,2,2-triphenylethenyl)phenoxy]-, 1,1-dimethylethyl ester](/data/chemimg/3781500/1637381-91-9.png)
![Acetic acid, 2-[4-(1,2,2-triphenylethenyl)phenoxy]-, 1,1-dimethylethyl ester](/data/chemimg/3781500/1637381-91-9_b.png)
![Acetic acid, 2-[4-(1,2,2-triphenylethenyl)phenoxy]-](/data/chemimg/3781500/1471339-65-7.png)
![Acetic acid, 2-[4-(1,2,2-triphenylethenyl)phenoxy]-](/data/chemimg/3781500/1471339-65-7_b.png)
![Ethanol, 2-[2-[(2-oxido-1,3,2-dioxaphospholan-2-yl)oxy]ethoxy]-, homopolymer, 3',3'-dimethyl-6-nitrospiro[2H-1-benzopyran-2,2'-[2H]indole]-1'(3'H)-](/data/chemimg/3779800/1393824-46-8.png)
![Ethanol, 2-[2-[(2-oxido-1,3,2-dioxaphospholan-2-yl)oxy]ethoxy]-, homopolymer, 3',3'-dimethyl-6-nitrospiro[2H-1-benzopyran-2,2'-[2H]indole]-1'(3'H)-](/data/chemimg/3779800/1393824-46-8_b.png)
![2-Propenoic acid, 2-[(2-hydroxyethyl)dithio]ethyl ester](/data/chemimg/3781500/1373514-32-9.png)
![2-Propenoic acid, 2-[(2-hydroxyethyl)dithio]ethyl ester](/data/chemimg/3781500/1373514-32-9_b.png)
![N-[(E)-[1-[(2S,4S)-4-[(2R,4S,5S,6S)-4-AMINO-5-HYDROXY-6-METHYLOXAN-2-YL]OXY-2,5,12-TRIHYDROXY-7-METHOXY-6,11-DIOXO-3,4-DIHYDRO-1H-TETRACEN-2-YL]-2-HYDROXYETHYLIDENE]AMINO]-6-(2,5-DIOXOPYRROL-1-YL)HEXANAMIDE](http://img.cochemist.com/ccimg/1361700/1361644-26-9.png)
![N-[(E)-[1-[(2S,4S)-4-[(2R,4S,5S,6S)-4-AMINO-5-HYDROXY-6-METHYLOXAN-2-YL]OXY-2,5,12-TRIHYDROXY-7-METHOXY-6,11-DIOXO-3,4-DIHYDRO-1H-TETRACEN-2-YL]-2-HYDROXYETHYLIDENE]AMINO]-6-(2,5-DIOXOPYRROL-1-YL)HEXANAMIDE](http://img.cochemist.com/ccimg/1361700/1361644-26-9_b.png)
![Propanoic acid, 2-bromo-2-methyl-, 2-[(2-hydroxyethyl)dithio]ethyl ester](/data/chemimg/142800/1228427-76-6.png)
![Propanoic acid, 2-bromo-2-methyl-, 2-[(2-hydroxyethyl)dithio]ethyl ester](/data/chemimg/142800/1228427-76-6_b.png)
![2-Propenoic acid, 2-methyl-, 2-[(2-hydroxyethyl)dithio]ethyl ester](/data/chemimg/147300/1205532-50-8.png)
![2-Propenoic acid, 2-methyl-, 2-[(2-hydroxyethyl)dithio]ethyl ester](/data/chemimg/147300/1205532-50-8_b.png)
![2-Propenoic acid, 2-methyl-, 2-[(4-methyl-2-oxo-2H-1-benzopyran-7-yl)oxy]ethyl ester](/data/chemimg/132800/928653-14-9.png)
![2-Propenoic acid, 2-methyl-, 2-[(4-methyl-2-oxo-2H-1-benzopyran-7-yl)oxy]ethyl ester](/data/chemimg/132800/928653-14-9_b.png)
![1-Decanol, 10-[(3b)-cholest-5-en-3-yloxy]-](http://img.cochemist.com/ccimg/354900/354812-89-8.png)
![1-Decanol, 10-[(3b)-cholest-5-en-3-yloxy]-](http://img.cochemist.com/ccimg/354900/354812-89-8_b.png)
![4-Amino-1-[(5S)-5-(hydroxymethyl)tetrahydro-2-furanyl]-2(1H)-pyri midinone](http://img.cochemist.com/ccimg/83900/83869-56-1.png)
![4-Amino-1-[(5S)-5-(hydroxymethyl)tetrahydro-2-furanyl]-2(1H)-pyri midinone](http://img.cochemist.com/ccimg/83900/83869-56-1_b.png)
![1-Hexanol, 6-[[(3b)-cholest-5-en-3-yl]oxy]-](http://img.cochemist.com/ccimg/68400/68354-84-7.png)
![1-Hexanol, 6-[[(3b)-cholest-5-en-3-yl]oxy]-](http://img.cochemist.com/ccimg/68400/68354-84-7_b.png)
![Spiro[2H-1-benzopyran-2,2'-[2H]indole]-1'(3'H)-propanoic acid, 3',3'-dimethyl-6-nitro-](/data/chemimg/583600/55779-26-5.png)
![Spiro[2H-1-benzopyran-2,2'-[2H]indole]-1'(3'H)-propanoic acid, 3',3'-dimethyl-6-nitro-](/data/chemimg/583600/55779-26-5_b.png)
![2-[4-(aminoiminomethyl)phenyl]-1H-Indole-6-carboximidamide](http://img.cochemist.com/ccimg/47200/47165-04-8.png)
![2-[4-(aminoiminomethyl)phenyl]-1H-Indole-6-carboximidamide](http://img.cochemist.com/ccimg/47200/47165-04-8_b.png)
![Ethanaminium,2-[[(dodecyloxy)hydroxyphosphinyl]oxy]-N,N,N-trimethyl-, inner salt](http://img.cochemist.com/ccimg/29600/29557-51-5.png)
![Ethanaminium,2-[[(dodecyloxy)hydroxyphosphinyl]oxy]-N,N,N-trimethyl-, inner salt](http://img.cochemist.com/ccimg/29600/29557-51-5_b.png)
![Poly[oxy(1-oxo-1,6-hexanediyl)]](http://img.cochemist.com/ccimg/25300/25248-42-4.png)
![Poly[oxy(1-oxo-1,6-hexanediyl)]](http://img.cochemist.com/ccimg/25300/25248-42-4_b.png)
![5H-Benzo[a]phenoxazin-5-one,9-(diethylamino)-](http://img.cochemist.com/ccimg/7400/7385-67-3.png)
![5H-Benzo[a]phenoxazin-5-one,9-(diethylamino)-](http://img.cochemist.com/ccimg/7400/7385-67-3_b.png)
](http://img.cochemist.com/ccimg/27000/26913-06-4.png)
](http://img.cochemist.com/ccimg/27000/26913-06-4_b.png)
