Co-reporter:Yang Hu, Chun Wen, Lizhi Song, Nana Zhao, Fu-Jian Xu
Journal of Controlled Release 2017 Volume 255(Volume 255) pp:
Publication Date(Web):10 June 2017
DOI:10.1016/j.jconrel.2017.04.001
The development of new hetero-nanostructures for multifunctional applications in cancer therapy has attracted widespread attention. In this work, we put forward a facile approach to synthesize multifunctional hetero-nanostructures of cellulose nanocrystal (CNC)-gold nanoparticle hybrids wrapped with low-toxic hydroxyl-rich polycations to integrate versatile functions for effective cancer therapy. Biocompatible CNCs with the superior rod-like morphology for high cellular uptake were employed as substrates to flexibly load spherical gold nanoparticles (Au NPs) or gold nanorods (Au NRs) through gold-thiolate bonds, producing hetero-layered nanohybrids of CNC-Au NPs or CNC-Au NRs. Profound hydroxyl-rich cationic gene carrier, CD-PGEA (comprising β-cyclodextrin cores and ethanolamine-functionalized poly(glycidyl methacrylate) arms), was then assembled onto the surface of CNC-Au nanohybrids through host-guest interaction and gold-thiolate bonds, where PEG was employed as the intermediate and spacer. The resultant CNC-Au-PGEA hetero-nanostructures exhibited excellent performances as gene carriers. Furthermore, CNC-Au NR-PGEA comprising Au NRs demonstrated favorable optical absorption properties and were validated for photoacoustic imaging and combined photothermal/gene therapy with considerable antitumor effects. The present work provided a flexible strategy for the construction of new multifunctional hetero-nanostructures with high antitumor efficacy.Download high-res image (220KB)Download full-size image
Co-reporter:Rui-Quan Li;Yanli Ren;Wenjuan Liu;Wenting Pan;Ming Yang
Nanoscale (2009-Present) 2017 vol. 9(Issue 7) pp:2521-2530
Publication Date(Web):2017/02/16
DOI:10.1039/C6NR09668A
Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies worldwide. Long noncoding RNA (lncRNA) MALAT1 acts as an essential oncogene lncRNA (onco-lncRNA) in the development of ESCC. Down-regulation of onco-lncRNA MALAT1 mediated by microRNA-101 (miR-101) and microRNA-217 (miR-217) has been proved to effectively suppress ESCC. In this study, poly(glycidyl methacrylate)-based star-like polycations with flanking folic acid (FA) ligands and rich hydrophilic hydroxyl groups (denoted as s-PGEA-FA) were proposed as efficient nanovectors to deliver miR-101 and miR-217 for silencing onco-lncRNA MALAT1 in different ESCC cells. The inhibition of ESCC by s-PGEA-FA/miRNA nanocomplexes would be achieved via subsequently targeting onco-lncRNA MALAT1 in ESCC cells. To evaluate the ESCC tumor-suppressing efficacy mediated by s-PGEA-FA/miRNA nanocomplexes, a series of assays were carried out, including gene transfection, cell proliferation, cell migration, and cell invasion. The results revealed that s-PGEA-FA-mediated miR-101 and miR-217 delivery effectively inhibited ESCC development, indicating the s-PGEA-FA nanovector was promising for future ESCC therapy.
Co-reporter:Lizhi Song;Nana Zhao
Advanced Functional Materials 2017 Volume 27(Issue 32) pp:
Publication Date(Web):2017/08/01
DOI:10.1002/adfm.201701255
It is of great significance to develop a multifunctional imaging-guided therapeutic platform with ideal resolution and sensitivity. Notably, rare-earth (RE) nanoparticles are attractive candidates for multimodal imaging due to their unique optical and magnetic properties. In this work, a rational design of hierarchical nanohybrids employing RE-Au hetero-nanostructures is proposed. 1D RE nanorods are adopted as the core to facilitate cellular internalization with the coating of gold nanoshells for photothermal performances. Hydroxyl-rich polycations with low cytotoxicity are grafted onto the surface of RE-Au to produce RE-Au-PGEA (ethanolamine-functionalized poly(glycidyl methacrylate)) nanohybrids with impressive gene transfection capability. Given the virtues of all the components, the feasibility of RE-Au-PGEA for multifunctional photoacoustic, computed tomography, magnetic resonance, upconversion luminescence imaging, and complementary photothermal therapy/gene therapy therapy is investigated in detail in vitro and in vivo. The visualization of the therapeutic processes with comprehensive information renders RE-Au-PGEA nanohybrid an intriguing platform to realize enhanced antitumor efficiency.
Co-reporter:Ranran Wang;Nana Zhao
Advanced Functional Materials 2017 Volume 27(Issue 23) pp:
Publication Date(Web):2017/06/01
DOI:10.1002/adfm.201700256
Gold nanoparticles exhibiting absorption in the desirable near-infrared region are attractive candidates for photothermal therapy (PTT). Furthermore, the construction of one nanoplatform employing gold nanoparticles for complementary therapy is still a great challenge. Here, well-defined unique hollow silica nanostars with encapsulated gold caps (starlike Au@SiO2) are readily synthesized using a sacrificial template method. Ethanolamine-functionalized poly(glycidyl methacrylate) (denoted as BUCT-PGEA) brushes are then grafted controllably from the surface of starlike Au@SiO2 nanoparticles via surface-initiated atom transfer radical polymerization to produce starlike Au@SiO2-PGEA. The photothermal effect of gold caps with a cross cavity can be utilized for PTT. The interior hollow feature of starlike Au@SiO2 nanoparticles endows them with excellent drug loading capability for chemotherapy, while the polycationic BUCT-PGEA brushes on the surface provide good transfection performances for gene therapy, which will overcome the penetration depth limitation of PTT for tumor therapy. Compared with ordinary spherical Au@SiO2-PGEA counterparts, the starlike Au@SiO2-PGEA hybrids with sharp horns favor endocytosis, which can contribute to enhanced antitumor effectiveness. The rational integration of photothermal gold caps, hollow nanostars, and polycations through the facile strategy might offer a promising avenue for complementary cancer therapy.
Co-reporter:Yang Hu, Yang Li, and Fu-Jian Xu
Accounts of Chemical Research 2017 Volume 50(Issue 2) pp:
Publication Date(Web):January 9, 2017
DOI:10.1021/acs.accounts.6b00477
ConspectusBecause of their biocompatibility, biodegradability, and unique bioactive properties, polysaccharides have been recognized and directly applied as excellent candidates for various biomedical applications. In order to introduce more functionalities onto polysaccharides, various modification methods were applied to improve the physical-chemical and biochemical properties. Grafting polysaccharides with functional polymers with limited reaction sites maximizes the structural integrity. To the best of our knowledge, great efforts have been made by scientists across the world, including our research group, to explore different strategies for the synthesis and design of controllable polymer-grafted polysaccharides. By the application of some reasonable strategies, a series of polymer-grafted polysaccharides with satisfactory biocharacteristics were obtained. The first strategy involves facile modification of polysaccharides with living radical polymerization (LRP). Functionalized polysaccharides with diverse grafts can be flexibly and effectively achieved. The introduced grafts include cationic components for nuclei acid delivery, PEGylated and zwitterionic moieties for shielding effects, and functional species for bioimaging applications as well as bioresponsive drug release applications. The second synthetic model refers to biodegradable polymer-grafted polysaccharides prepared by ring-opening polymerization (ROP). Inspired by pathways to introduce initiation sites onto polysaccharides, the use of amine-functionalized polysaccharides was explored in-depth to trigger ROP of amino acids. A series of poly(amino acid)-grafted polysaccharides with advanced structures (including linear, star-shaped, and comb-shaped copolymers) were developed to study and optimize the structural effects. In addition, biodegradable polyester-grafted polysaccharides were prepared and utilized for drug delivery. Another emerging strategy was to design polysaccharide-based assemblies with supramolecular structures. A variety of assembly techniques using non-covalent interactions were established to construct different types of polysaccharide-based assemblies with various bioapplications.On the basis of these strategies, polymer-grafted polysaccharides with controllable functions were reported to be well-suited for different kinds of biomedical applications. The exciting results were obtained from both in vitro and in vivo models. Viewing the rapid growth of this field, the present Account will update the concepts, trends, perspectives, and applications of functionalized polysaccharides, guiding and inspiring researchers to explore new polysaccharide-based systems for wider applications.
Co-reporter:Yeping Wu, Anzhi Wang, Xiaokang Ding, and Fu-Jian Xu
ACS Applied Materials & Interfaces 2017 Volume 9(Issue 1) pp:
Publication Date(Web):December 13, 2016
DOI:10.1021/acsami.6b12033
The development of new materials for fast and sensitive protease assay is in demand for timely diagnosis of diseases, such as cardiovascular disease, cancers, and Alzheimer disease. Herein, poly(methacrylic acid) (PMAA) brushes were synthesized from the surfaces of silica nanoparticles via surface-initiated atom transfer radical polymerization (ATRP), and functionalized with series of proteolytically cleavable peptides for highly sensitive protease assay. Upon the proteolytic cleavage of the peptides, a short peptide fragment with fluorescent tag (GGK-FITC) is released to the solution, which can be easily detected with a benchtop fluorescence microscope. The grafting densities of PMAA brushes and peptides can be readily tuned by controlling the monomer concentrations of sodium methacrylate in the ATRP reaction. Because of the three-dimensional architecture of PMAA brushes, the loading amount of peptides can reach 21.4% of the total weight of functionalized silica particles (22.4 peptides/nm2), which is much higher than direct immobilization on silica nanoparticles without polymer brushes. Because of the high loading density of peptides, the limit of detection (LOD) of trypsin can reach 1.4 pM in buffer solution or 2.6 nM in nondiluted serum. By rational design of peptide substrates, the peptide-functionalized PMAA brushes can be readily expanded to detect other proteases, such as matrix metalloproteinase-2 (MMP-2), a virtual biomarker for many cancers, with an LOD of 1.1 pM. The proteolytically cleavable peptide-functionalized PMAA brushes offer a starting point for fast and sensitive protease assay.Keywords: ATRP; peptide; PMAA; polymer brush; protease assay;
Co-reporter:Huimin Yuan;Chen Xu;Yu Zhao;Bingran Yu;Gang Cheng
Advanced Functional Materials 2016 Volume 26( Issue 17) pp:2855-2865
Publication Date(Web):
DOI:10.1002/adfm.201504980
Protein-based nanoparticles are widely used for effective biomedical applications. The objective of this work is to design series of magnetic resonance imaging (MRI)-visible cationic supramolecular nanoparticles (PGEA@BSA-Ad/Gd3+) based on bovine serum albumin (BSA) and β-cyclodextrin-cored star ethanolamine-functionalized poly(glycidyl methacrylate) (CD-PGEA) in the presence of Gd3+ ions for multifunctional delivery systems. CD-PGEA is prepared via atom transfer radical polymerization and ring-opening reaction. It is found that in the absence of Gd3+ ions, CD-PGEA does not well interact with adamantine-modified BSA (BSA-Ad). The well-defined PGEA@BSA-Ad/Gd3+ supramolecular nanoparticles could be produced through the synergistic actions of the host–guest and electrostatic self-assemblies by mixing aqueous solutions of CD-PGEA, BSA-Ad, and Gd3+. In comparison with CD-PGEA assembly units, such kinds of uniform PGEA@BSA-Ad/Gd3+ supramolecular nanoparticles exhibit better pDNA condensation ability, lower cytotoxicity, higher gene transfection, and easier cellular uptake. In addition, PGEA@BSA-Ad/Gd3+ also produces outstanding MRI abilities, much better than Magnevist (Gd-diethylenetriaminepentacetate acid). The present design of protein–polymer supramolecular nanoparticles with MRI contrast agents would provide a new way for multifunctional gene/drug delivery systems.
Co-reporter:Nana Zhao;Jia Li;Yiqiang Zhou;Yang Hu;Ranran Wang;Zhaoxia Ji;Fusheng Liu
Advanced Functional Materials 2016 Volume 26( Issue 32) pp:5848-5861
Publication Date(Web):
DOI:10.1002/adfm.201601418
Organic/inorganic nanohybrids hold great importance in fabricating multifunctional theranostics to integrate therapeutic functions with real-time imaging. Although Au nanorods (NRs) have been employed for theranostics, complicated design of materials limits their practical applications. In this work, new multifunctional theranostic agents are designed and synthesized employing Au NRs with desirable near-infrared absorbance as the cores. A facile “grafting-onto” approach is put forward to prepare the series of hierarchical nanohybrids (Au-PGEA and Au-PGED) of Au NRs and poly(glycidyl methacrylate)-based polycations. The resultant nanohybrids can be utilized as gene carriers with high gene transfection performances. The structural effect of polycations on gene transfection is investigated in detail, and Au-PGEA with abundant hydroxyl groups on the surface exhibits superior performance. Au-PGEA nanohybrids are further validated to possess remarkable capability of combined photothermal therapy (PTT) and gene therapy (GT) for complementary tumor treatment. Moreover, significantly enhanced computed tomography (CT)/photoacoustic (PA) signals are detected both in vitro and in vivo, verifying the potential of Au-PGEA for dual-modal imaging with precise and accurate information. Therefore, these multifunctional nanohybrids fabricated from a simple and straightforward strategy are promising for in vivo dual-modal CT/PA imaging guided GT/PTT therapy with high antitumor efficacy.
Co-reporter:Yajun Huang, Hao Hu, Rui-Quan Li, Bingran Yu, and Fu-Jian Xu
ACS Applied Materials & Interfaces 2016 Volume 8(Issue 6) pp:3919
Publication Date(Web):January 27, 2016
DOI:10.1021/acsami.5b11016
Owing to the low cytotoxicity and excellent biocompatibility, polysaccharides are good candidates for the development of promising biomaterials. In this paper, a series of magnetic resonance imaging (MRI)-visible cationic polymeric nanoparticles involving liver cell-targeting polysaccharides were flexibly designed for multifunctional gene delivery systems. The pullulan-based vector (PuPGEA) consisting of one liver cell-targeting pullulan backbone and ethanolamine-functionalized poly(glycidyl methacrylate) (denoted by BUCT-PGEA) side chains with abundant hydroxyl units and secondary amine was first prepared by atom transfer radical polymerization. The resultant cationic nanoparticles (PuPGEA-GdL or PuPGEA-GdW) with MRI functions were produced accordingly by assembling PuPGEA with aminophenylboronic acid-modified Gd-DTPA (GdL) or GdW10O369– (GdW) via the corresponding etherification or electrostatic interaction. The properties of the PuPGEA-GdL and PuPGEA-GdW nanoparticles including pDNA condensation ability, cytotoxicity, gene transfection, cellular uptake, and in vitro and in vivo MRI were characterized in details. Such kinds of cationic nanoparticles exhibited good performances in gene transfection in liver cells. PuPGEA-GdW demonstrated much better MRI abilities. The present design of PuPGEA-based cationic nanoparticles with the liver cell-targeting polysaccharides and MRI contrast agents would shed light on the exploration of tumor-targetable multifunctional gene delivery systems.Keywords: cationic nanoparticle; gene delivery; MRI; PGMA; pullulan
Co-reporter:Ranran Wang, Yang Hu, Nana Zhao, and Fu-Jian Xu
ACS Applied Materials & Interfaces 2016 Volume 8(Issue 18) pp:11298
Publication Date(Web):April 21, 2016
DOI:10.1021/acsami.6b01697
Due to their unique properties, one-dimensional (1D) magnetic nanostructures are of great significance for biorelated applications. A facile and straightforward strategy to fabricate 1D magnetic structure with special shapes is highly desirable. In this work, well-defined peapod-like 1D magnetic nanoparticles (Fe3O4@SiO2, p-FS) are readily synthesized by a facile method without assistance of any templates, magnetic string or magnetic field. There are few reports on 1D gene carriers based on Fe3O4 nanoparticles. BUCT–PGEA (ethanolamine-functionalized poly(glycidyl methacrylate) is subsequently grafted from the surface of p-FS nanoparticles by atom transfer radical polymerization to construct highly efficient gene vectors (p-FS–PGEA) for effective biomedical applications. Peapod-like p-FS nanoparticles were proven to largely improve gene transfection performance compared with ordinary spherical Fe3O4@SiO2 nanoparticles (s-FS). External magnetic field was also utilized to further enhance the transfection efficiency. Moreover, the as-prepared p-FS–PGEA gene carriers could combine the magnetic characteristics of p-FS to well achieve noninvasive magnetic resonance imaging (MRI). We show here novel and multifunctional magnetic nanostructures fabricated for biomedical applications that realized efficient gene delivery and real-time imaging at the same time.Keywords: gene transfection; magnetic nanoparticles; MRI imaging; peapod-like; polycation
Co-reporter:Shun Duan, Bingran Yu, Chunxiao Gao, Wei Yuan, Jie Ma, and Fu-Jian Xu
ACS Applied Materials & Interfaces 2016 Volume 8(Issue 43) pp:29334
Publication Date(Web):October 11, 2016
DOI:10.1021/acsami.6b11029
For effective gene therapy, nonviral gene carriers with low toxicity and high transfection efficiency are of much importance. In this work, we developed a facile strategy to prepare hyperbranched hydroxyl-rich polycations (denoted by TE) by the one-pot method involving ring-opening reactions between two commonly used reagents, ethylenediamine (ED) with two amino groups and 1,3,5-triglycidyl isocyanurate (TGIC) with three epoxy groups. The hyperbranched TEs with different molecular weights were investigated on their DNA condensation ability, protein absorption property, biocompatibility, transfection efficiency, and in vivo cancer therapy and toxicity. TE exhibited low cytotoxicity and protein absorption property due to the plentiful hydroxyl groups. The optimal transfection efficiency of TE was significantly higher than that of the gold standard polycationic gene carrier branched polyethylenimine (PEI, 25 kDa). Furthermore, TE was applied for in vivo tumor inhibition by the delivery of antioncogene p53, which showed good antitumor efficiency with low adverse effects. The present work provides a new concept for the facile preparation of hyperbranched hydroxyl-rich polycationic carriers with good transfection performances.Keywords: carrier; gene therapy; hydroxyl-rich; hyperbranched; ring-opening
Co-reporter:Jing-Jun Nie, Weiyi Zhao, Hao Hu, Bingran Yu, and Fu-Jian Xu
ACS Applied Materials & Interfaces 2016 Volume 8(Issue 13) pp:8376
Publication Date(Web):March 7, 2016
DOI:10.1021/acsami.6b00649
Polysaccharide-based copolymers have attracted much attention due to their effective performances. Heparin, as a kind of polysaccharide with high negative charge densities, has attracted much attention in biomedical fields. In this work, we report a flexible way to adjust the solubility of heparin from water to oil via the introduction of tetrabutylammonium groups for further functionalization. A range of heparin-based comb copolymers with poly(poly(ethylene glycol) methyl ether methacrylate) (PPEGMEMA), poly(dimethylaminoethyl methacrylate) (PDMAEMA), or PPEGMEMA-b-PDMAEMA side chains were readily synthesized in a MeOH/dimethylsulfoxide mixture via atom-transfer radical polymerization. The heparin-based polymer nanoparticles involving cationic PDMAEMA were produced due to the electrostatic interaction between the negatively charged heparin backbone and PDMAEMA grafts. Then the pDNA condensation ability, cytotoxicity, and gene transfection efficiency of the nanoparticles were characterized in comparison with the reported gene vectors. The nanoparticles were proved to be effective gene vectors with low cytotoxicity and high transfection efficiency. This study demonstrates that by adjusting the solubility of heparin, polymer graft functionalization of heparin can be readily realized for wider applications.Keywords: ATRP; functionalization; heparin; nanoparticles; polysaccharide
Co-reporter:Rui-Quan Li, Wei Wu, Hai-Qing Song, Yanli Ren, Ming Yang, Jianshu Li, Fu-Jian Xu
Acta Biomaterialia 2016 Volume 41() pp:282-292
Publication Date(Web):1 September 2016
DOI:10.1016/j.actbio.2016.06.006
Abstract
Nucleic acid-based gene therapy is a promising treatment option to cure numerous intractable diseases. For non-viral gene carriers, low-molecular-weight polymeric vectors generally demonstrate poor transfection performance, but benefit their final removals from the body. Recently, it was reported that aminated poly(glycidyl methacrylate) (PGMA) is one potential gene vector. Based on ethylenediamine (ED)-functionalized low-molecular-weight PGMA (denoted by PGED), a flexible strategy was herein proposed to design new well-defined reducible cationic nanogels (denoted by PGED-NGs) with friendly crosslinking reagents for highly efficient nucleic acid delivery. α-Lipoic acid (LA), one natural antioxidant in human body, was readily introduced into ED-functionalized PGMA and crosslinked to produce cationic PGED-NGs with plentiful reducible lipoyl groups. PGED-NGs could effectively complex plasmid DNA (pDNA) and short interfering RNA (siRNA). Compared with pristine PGED, PGED-NGs exhibited much better performance of pDNA transfection. PGED-NGs also could efficiently transport MALAT1 siRNA (siR-M) into hepatoma cells and significantly suppressed the cancer cell proliferation and migration. The present work indicated that reducible cationic nanogels involving LA crosslinking reagents are one kind of competitive candidates for high-performance nucleic acid delivery systems.
Statement of Significance
Recently, the design of new types of high-performance nanoparticles is of great significance in delivering therapeutics. Nucleic acid-based therapy is a promising treatment option to cure numerous intractable diseases. A facile and straightforward strategy to fabricate safe nucleic acid delivery nanovectors is highly desirable. In this work, based on ethylenediamine-functionalized low-molecular-weight poly(glycidyl methacrylate), a flexible strategy was proposed to design new well-defined reducible cationic nanogels (denoted by PGED-NGs) with α-Lipoic acid, one friendly crosslinking reagent, for highly efficient nucleic acid delivery. Such PGED-NGs possess plentiful reducible lipoyl groups, effectively encapsulated pDNA and siRNA and exhibited excellent abilities of nucleic acid delivery. The present work indicated that reducible cationic nanogels involving α-lipoic acid crosslinking reagents are one kind of competitive candidates for high-performance nucleic acid delivery systems.
Co-reporter:Chun Wen, Yang Hu, Chen Xu, Fu-Jian Xu
Acta Biomaterialia 2016 Volume 32() pp:110-119
Publication Date(Web):1 March 2016
DOI:10.1016/j.actbio.2015.12.033
Abstract
Supramolecular cyclodextrin polyrotaxane (PR) has attracted much attention due to their unique flexible properties. In this work, the reducible PR-based cationic block copolymer (SS-PR) was prepared via ATRP of DMAEMA based on the self-assembled pseudo-PR. A series of pseudo-comb polycations (SS-PR-pDM) with different molecular weights were subsequently produced via two-step ATRP of DMAEMA by using bromoisobutylryl-functionalized SS-PR as the macroinitiator. Incorporation of disulfide linkages in the backbone of PR permits the SS-PR and pseudo-comb SS-PR-pDM to be readily disassembled upon reductive stimuli. SS-PR-pDM exhibited the enhanced pDNA-condensing ability and similarly low toxicity compared with SS-PR. Meanwhile, SS-PR-pDM displayed higher cell internalization rates (88% for SS-PR-pDM3 vs. 77% for SS-PR) and luciferase gene transfection efficiency. The percentages of the EGFP-positive HeLa cells mediated by SS-PR-pDM3 and SS-PR were 44% and 22%, respectively. Furthermore, the favorable property of the pseudo-comb SS-PR-pDM benefited pDNA entering the nucleus. The present work demonstrates that properly grafting cationic side chains from reducible PR backbones via consecutive ATRP processes was one effective means to produce new PR-based supramolecular polycations.
Statement of Significance
Supramolecular cyclodextrin polyrotaxanes (PR) had been attracted much attention due to their unique flexible properties. In this work, two kinds of bioreducible PR-based polycations were synthesized via consecutive ATRP processes for gene delivery. The bioreducible PR-based cationic block copolymer (SS-PR) was prepared via ATRP of DMAEMA based on the self-assembled pseudopolyrotaxane of α-cyclodextrins (α-CD) with a disulfide-linked bromoisobutylryl-terminated PEG. Then, a series of pseudo-comb polycations (SS-PR-pDM) with different molecular weights were subsequently produced by using SS-PR-Br macroinitiators via step-two ATRP of DMAEMA. Incorporation of disulfide linkages in bromoisobutylryl-terminated PEG permits the SS-PR and pseudo-comb SS-PR-pDM to be readily disassembled upon reductive stimuli, contributing to gene delivery efficiency. SS-PR-pDM displayed higher cell internalization and gene transfection efficiency. In addtion, the favorable property of the pseudo-comb SS-PR-pDM benefited pDNA entering the nucleus. The present work demonstrates that properly grafting pDMAEMA side chains from bioreducible polyrotaxane backbones via consecutive ATPR processes was one effective means to produce new PR-based supramolecular polycations.
Co-reporter:Miao Qi, Shun Duan, Bingran Yu, Hao Yao, Wei Tian and Fu-Jian Xu
Polymer Chemistry 2016 vol. 7(Issue 26) pp:4334-4341
Publication Date(Web):18 May 2016
DOI:10.1039/C6PY00759G
Supramolecular chemistry has been widely applied in biomedical fields. It was reported that the topological structure has effects on the performance of gene delivery systems. Supramolecular polymer-like gene carriers with hyperbranched topological structures have still not been reported. In this work, a series of ethanolamine-functionalized polyglycidyl methacrylate (PGMA)-armed AB2 type macromonomers were synthesized based on atom transfer radical polymerization. The AB2 type macromonomers can self-assemble into supramolecular hyperbranched polymers by the host–guest interaction between adamantane and β-cyclodextrin. The biophysical properties of self-assembled and dissembled supramolecular hyperbranched polycations were evaluated in detail. The self-assembled supramolecular polycations with hyperbranched structures possessed higher pDNA condensation ability and much better gene transfection performances than the dissembled AB2 type counterparts. The present work would provide a new venue for designing advanced high-performance supramolecular hyperbranched nucleic acid-delivery systems.
Co-reporter:Hao Hu, Xiu-Ju Hou, Xiao-Chen Wang, Jing-Jun Nie, Qing Cai and Fu-Jian Xu
Polymer Chemistry 2016 vol. 7(Issue 18) pp:3107-3116
Publication Date(Web):07 Apr 2016
DOI:10.1039/C6PY00251J
Non-spherical nanoparticles have been proven to be promising materials for drug delivery systems. Spindly cellulose nanocrystals (CNCs) are one kind of natural organic nanoparticles with good biocompatibility and unique physico-chemical properties. In this work, gold (Au) nanoparticle-conjugated heterogeneous polymer brush-coated CNCs were prepared via different controllable polymerization techniques for effective biomedical applications. One bi-functional CNC-based initiator was first prepared to initiate both atom transfer radical polymerization (ATRP) and reversible addition–fragmentation chain transfer (RAFT) polymerization. Poly(poly(ethylene glycol)ethyl ether methacrylate) (PPEGEEMA) and poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) brushes were individually grafted from CNCs. The cationic PDMAEMA chains complex genes effectively, while the uncharged PPEGEEMA brushes spread outwards and reduce the cytotoxicity significantly. In order to impart computed tomography (CT) imaging function to CNCs, Au nanoparticles as CT contrast agents were in situ formed on the CNC-based carriers by using the amine groups of PDMAEMA chains as reducing and protective agents. The in vitro CT imaging, gene condensation ability, cytotoxicity, gene transfection, and cellular uptake of CNC-based vectors were investigated in detail. Such effective CNC-based gene vectors with gold nanoparticle-conjugated heterogeneous polymer brushes would provide a promising multifunctional therapy system.
Co-reporter:Yue Sun, Hao Hu, Bingran Yu, and Fu-Jian Xu
Bioconjugate Chemistry 2016 Volume 27(Issue 11) pp:2744
Publication Date(Web):October 6, 2016
DOI:10.1021/acs.bioconjchem.6b00509
It is crucial for successful gene delivery to develop safe, effective, and multifunctional polycations. Iodine-based small molecules are widely used as contrast agents for CT imaging. Herein, a series of star-like poly(glycidyl methacrylate) (PGMA)-based cationic vectors (II-PGEA/II) with abundant flanking polyhydric iodine units are prepared for multifunctional gene delivery systems. The proposed II-PGEA/II star vector is composed of one iohexol intermediate (II) core and five ethanolamine (EA) and II-difunctionalized PGMA arms. The amphipathic II-PGEA/II vectors readily self-assemble into well-defined cationic nanoparticles, where massive hydroxyl groups can establish a hydration shell to stabilize the nanoparticles. The II introduction improves cell viabilities of polycations. Moreover, by controlling the suitable amount of introduced II units, the resultant II-PGEA/II nanoparticles can produce fairly good transfection performances in different cell lines. Particularly, the II-PGEA/II nanoparticles induce much better in vitro CT imaging abilities in tumor cells than iohexol (one commonly used commercial CT contrast agent). The present design of amphipathic PGMA-based nanoparticles with CT contrast agents would provide useful information for the development of new multifunctional gene delivery systems.
Co-reporter:Chen Xu, Bingran Yu, Hao Hu, Muhammad Naeem Nizam, Wei Yuan, Jie Ma and Fu-Jian Xu
Biomaterials Science 2016 vol. 4(Issue 8) pp:1233-1243
Publication Date(Web):04 Jul 2016
DOI:10.1039/C6BM00360E
Lipids, as the greatest constituent in cell membranes, have been widely used for biomedical applications because of their excellent biological properties. The introduction of membrane lipid molecules into gene vectors would embody greater biocompatibility, cellular uptake and transfection efficiency. In this work, one flexible strategy for readily conjugating lipid molecules with polycations was proposed based on atom transfer radical polymerization to produce a series of cholesterol (CHO)- and phosphatidylinositol (PI)-terminated ethanolamine-functionalized poly(glycidyl methacrylate)s, namely CHO-PGEAs and PI-PGEAs, as effective gene carriers. CHO-PGEAs and PI-PGEAs truly demonstrated much better transfection performances compared to linear ethanolamine-functionalized poly(glycidyl methacrylate) (denoted as BUCT-PGEA) counterparts and traditional standard branched polythylenimine (PEI, 25 kDa). In addition, the good antitumor effects of CHO-PGEA and PI-PGEA were confirmed with suppressor tumor gene p53 systems in vitro and in vivo. The present work could provide a new strategy to develop effective cationic conjugation of lipid molecules for gene therapy.
Co-reporter:Fu-Jian Xu
Nanomedicine: Nanotechnology, Biology and Medicine 2016 Volume 12(Issue 2) pp:465
Publication Date(Web):February 2016
DOI:10.1016/j.nano.2015.12.056
Co-reporter:Yajuan Yang;Yu Qi;Min Zhu;Nana Zhao;Fujian Xu
Nano Research 2016 Volume 9( Issue 9) pp:2531-2543
Publication Date(Web):2016 September
DOI:10.1007/s12274-016-1139-1
Semiconductor quantum dots (QDs) are considered as ideal fluorescent probes owing to their intrinsic optical properties. It has been demonstrated that the size and shape of nanoparticles significantly influence their behaviors in biological systems. In particular, one-dimensional (1D) nanoparticles with larger aspect ratios are desirable for cellular uptake. Here, we explore a facile and green method to prepare novel 1D wormlike QDs@SiO2 nanoparticles with controlled aspect ratios, wherein multiple QDs are arranged in the centerline of the nanoparticles. Then, an excellent cationic gene carrier, ethanolamine-functionalized poly(glycidyl methacrylate) (denoted by BUCT-PGEA), was in-situ produced via atom transfer radical polymerization on the surface of the QDs@SiO2 nanoparticles to achieve stable surfaces (QDs@SiO2-PGEA) for effective bioapplications. We found that the wormlike QDs@SiO2-PGEA nanoparticles demonstrated much higher gene transfection performance than ordinary spherical counterparts. In addition, the wormlike nanoparticles with larger aspect ratio performed better than those with smaller ratio. Furthermore, the gene delivery processes including cell entry and plasmid DNA (pDNA) escape and transport were also tracked in real time by the QDs@SiO2-PGEA/pDNA complexes. This work realized the integration of efficient gene delivery and real-time imaging within one controlled 1D nanostructure. These constructs will likely provide useful information regarding the interaction of nanoparticles with biological systems.
Co-reporter:Yu Zhao, Shun Duan, Bingran Yu, Fu-Sheng Liu, Gang Cheng and Fu-Jian Xu
NPG Asia Materials 2015 7(7) pp:e197
Publication Date(Web):2015-07-01
DOI:10.1038/am.2015.67
Ethanolamine (EA) or ethylenediamine (ED)-functionalized poly(glycidyl methacrylate) (PGMA), namely PGEA or PGED, has recently been used as effective gene carriers because of their low cytotoxicity and high transfection efficiency. In this study, a series of PGMA-based supramolecular polycations (PGED-Gd@PGEAs) with magnetic resonance imaging (MRI) functions were readily constructed by assembling multiple adamantine-headed star PGEA (Ad-PGEA) units with a versatile PGED-CD-Gd backbone, which possessed numerous flanking β-cyclodextrin species and Gd3+ ions. The properties of different PGED-Gd@PGEA vectors were systematically characterized, including the plasmid DNA condensation ability, cytotoxicity, gene transfection efficiency, cellular uptake and MRI function. Such supramolecular gene vectors had lower toxicity than ‘gold standard’ polyethylenimine (PEI, 25 kDa). Furthermore, PGED-Gd@PGEAs exhibited significantly higher transfection efficiencies than PEI or the constituent units (PGED-CD-Gd and Ad-PGEA). The chelation of Gd3+ ions imparted the PGED-Gd@PGEA vectors with a good MRI ability without obvious adverse effects. The present design of PGMA-based supramolecular polycations with Gd3+ chelation would provide useful information for the development of low-toxicity and high-efficiency multifunctional gene delivery systems.
Co-reporter:Hai-Qing Song, Rui-Quan Li, Shun Duan, Bingran Yu, Hong Zhao, Da-Fu Chen and Fu-Jian Xu
Nanoscale 2015 vol. 7(Issue 13) pp:5803-5814
Publication Date(Web):26 Feb 2015
DOI:10.1039/C4NR07515C
Polypeptide-based degradable polyplexes attracted considerable attention in drug delivery systems. Polysaccharides including cyclodextrin (CD), dextran, and chitosan (CS) were readily grafted with cationic poly(aspartic acid)s (PAsps). To further enhance the transfection performances of PAsp-based polyplexes, herein, different types of ligand (folic acid, FA)-functionalized degradable polyplexes were proposed based on the PAsp-grafted chitosan–cyclodextrin conjugate (CCPE), where multiple β-CDs were tied on a CS chain. The FA-functionalized CCPE (i.e., CCPE-FA) was obtained via a host–guest interaction between the CD units of CCPE and the adamantane (Ad) species of Ad-modified FA (Ad-FA). The resulting CCPE/pDNA, CCPE-FA/pDNA, and ternary CCPE-FA/CCPE/pDNA (prepared by layer-by-layer assembly) polyplexes were investigated in detail using different cell lines. The CCPE-based polyplexes displayed much higher transfection efficiencies than the CS-based polyplexes reported earlier by us. The ternary polyplexes of CCPE-FA/CCPE/pDNA produced excellent gene transfection abilities in the folate receptor (FR)-positive tumor cells. This work would provide a promising means to produce highly efficient polyplexes for future gene therapy applications.
Co-reporter:Peng Yan, Ranran Wang, Nana Zhao, Hong Zhao, Da-Fu Chen and Fu-Jian Xu
Nanoscale 2015 vol. 7(Issue 12) pp:5281-5291
Publication Date(Web):16 Feb 2015
DOI:10.1039/C5NR00481K
Favorable physical and chemical properties endow Au nanoparticles (Au NPs) with various biomedical applications. After appropriate surface functionalization, Au NPs could construct promising drug/gene carriers with multiple functions. There is now ample evidence that physicochemical properties, such as size, shape, and surface chemistry, can dramatically influence the behaviors of Au NPs in biological systems. Investigation of these parameters could be fundamentally important for the application of Au NPs as drug/gene carriers. In this work, we designed a series of novel gene carriers employing polycation-functionalized Au NPs with five different morphologies (including Au nanospheres, Au nano-octahedra, arrow-headed Au nanorods, and Au nanorods with different aspect ratios). The effects of the particle size and shape of these different carriers on gene transfection were investigated in detail. The morphology of Au NPs is demonstrated to play an important role in gene transfection. The most efficient gene carriers are those fabricated with arrow-headed Au nanorods. Au nanosphere-based carriers exhibit the poorest performance in gene transfection. In addition, Au nanorods with smaller aspect ratios perform better than longer ones. These results may provide new avenues to develop promising gene carriers and gain useful information on the interaction of Au NPs with biological systems.
Co-reporter:Feng Yao, Hao Hu, Sailong Xu, Ruijie Huo, Zhiping Zhao, Fazhi Zhang, and Fujian Xu
ACS Applied Materials & Interfaces 2015 Volume 7(Issue 7) pp:3882
Publication Date(Web):February 5, 2015
DOI:10.1021/acsami.5b00145
We describe a reliable preparation of MgAl-layered double hydroxide (MgAl-LDH) micropatterned arrays on gold substrate by combining SO3–-terminated self-assembly monolayer and photolithography. The synthesis route is readily extended to prepare LDH arrays on the SO3–-terminated polymer-bonded glass substrate amenable for cell imaging. The anion-exchangeable MgAl-LDH micropattern can act both as bioadhesive region for selective cell adhesion and as nanocarrier for drug molecules to regulate cell behaviors. Quantitative analysis of cell adhesion shows that selective HepG2 cell adhesion and spreading are promoted by the micropatterned MgAl-LDH, and also suppressed by methotrexate drug released from the LDH interlayer galleries.Keywords: cell adhesion; in situ growth; layered double hydroxide; methotrexate; micropatterned arrays; photolithography
Co-reporter:Yan-Yu Yang, Hao Hu, Xing Wang, Fei Yang, Hong Shen, Fu-Jian Xu, and De-Cheng Wu
ACS Applied Materials & Interfaces 2015 Volume 7(Issue 22) pp:12238
Publication Date(Web):May 20, 2015
DOI:10.1021/acsami.5b02733
It was recently reported that ethanolamine-functionalized poly(glycidyl methacrylate) (PGEA) possesses great potential applications in gene therapy due to its good biocompatibility and high transfection efficiency. Importing responsivity into PGEA vectors would further improve their performances. Herein, a series of responsive star-shaped vectors, acetaled β-cyclodextrin-PGEAs (A-CD-PGEAs) consisting of a β-CD core and five PGEA arms linked by acid-labile acetal groups, were proposed and characterized as therapeutic pDNA vectors. The A-CD-PGEAs owned abundant hydroxyl groups to shield extra positive charges of A-CD-PGEAs/pDNA complexes, and the star structure could decrease charge density. The incorporation of acetal linkers endowed A-CD-PGEAs with pH responsivity and degradation. In weakly acidic endosome, the broken acetal linkers resulted in decomposition of A-CD-PGEAs and morphological transformation of A-CD-PGEAs/pDNA complexes, lowering cytotoxicity and accelerating release of pDNA. In comparison with control CD-PGEAs without acetal linkers, A-CD-PGEAs exhibited significantly better transfection performances.Keywords: acetal linker; acid-lability; biodegradation; gene vector; star-shaped;
Co-reporter:Jing-Jun Nie, Xue-Bo Dou, Hao Hu, Bingran Yu, Da-Fu Chen, Ren-Xian Wang, and Fu-Jian Xu
ACS Applied Materials & Interfaces 2015 Volume 7(Issue 1) pp:553
Publication Date(Web):December 1, 2014
DOI:10.1021/am506730t
Due to its good properties such as low cytotoxicity, degradability, and biocompatibility, poly(aspartic acid) (PAsp) is a good candidate for the development of new drug delivery systems. In this work, a series of new PAsp-based degradable supramolecular assemblies were prepared for effective gene therapy via the host–guest interactions between the cyclodextrin (CD)-cored PAsp-based polycations and the pendant benzene group-containing PAsp backbones. Such supramolecular assemblies exhibited good degradability, enhanced pDNA condensation ability, and low cytotoxicity. More importantly, the gene transfection efficiencies of supramolecular assemblies were much higher than those of CD-cored PAsp-based counterparts at various N/P ratios. In addition, the effective antitumor ability of assemblies was demonstrated with a suicide gene therapy system. The present study would provide a new means to produce degradable supramolecular drug delivery systems.Keywords: degradable; DNA; self-assembly; supramolecular; vector
Co-reporter:Hao Hu, Wei Yuan, Fu-Sheng Liu, Gang Cheng, Fu-Jian Xu, and Jie Ma
ACS Applied Materials & Interfaces 2015 Volume 7(Issue 16) pp:8942
Publication Date(Web):April 7, 2015
DOI:10.1021/acsami.5b02432
Carbon nanotubes have excellent penetrability and encapsulation efficiency in the fields of drug and gene delivery. Because of their excellent physicochemical properties, biocompatible rodlike cellulose nanocrystals (CNCs) were reportedly expected to replace carbon nanotubes. In this work, CNCs from natural cotton wool were functionalized with disulfide bond-linked poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) brushes for effective biomedical applications. A range of CNC-graft-PDMAEMA vectors (termed as CNC-SS-PDs) with various molecular weights of PDMAEMA were synthesized. Under reducible conditions, PDMAEMA chains can be easily cleaved from CNCs. The gene condensation ability, reduction sensitivity, cytotoxicity, gene transfection, and in vivo antitumor activities of CNC-SS-PDs were investigated in detail. The CNC-SS-PDs exhibited good transfection efficiencies and low cytotoxicities. The needlelike shape of CNCs had an important effect on enhancing transfection efficiency. The antitumor effect of CNC-SS-PDs was evaluated by a suicide gene/prodrug system (cytosine deaminase/5-fluorocytosine, CD/5-FC) in vitro and in vivo. This research demonstrates that the functionalization of CNCs with redox-responsive polycations is an effective method for developing novel gene delivery systems.Keywords: antitumor; ATRP; bioreducible; cellulose; gene transfection; PDMAEMA;
Co-reporter:Rui-Quan Li, Hai-Qing Song and Fu-Jian Xu
Polymer Chemistry 2015 vol. 6(Issue 34) pp:6208-6218
Publication Date(Web):14 Jul 2015
DOI:10.1039/C5PY00819K
Phenylboronic acid (PBA) possesses good affinities to glycoproteins on cell surfaces, as well as stable fluorescence properties. Recently, it was found that ethanolamine (EA)-decorated poly(glycidyl methacrylate) (PGMA), namely PGEA, exhibited promising applications as effective gene vectors. In this work, a strategy to prepare series of starlike PGEA vectors (s-PGEA-B) with flanking PBA groups was proposed for the development of highly efficient multifunctional gene delivery systems. Compared with the s-PGEA vectors without PBA groups, the corresponding s-PGEA-B counterparts showed a greater ability to bind pDNA. The sizes of the formed s-PGEA-B/pDNA nanoparticles were ∼100 nm at higher N/P ratios. The s-PGEA-B/pDNA complexes exhibited enhanced cellular internalization and transfection efficiencies, particularly in the cell lines with abundant cell surface glycoproteins. The cellular internalization mediated by s-PGEA-B with 30% of PBA content was about 85% in HepG2 cells, much higher than that of the corresponding s-PGEA (about 53%). In addition, the simultaneous fluorescence emitted from s-PGEA-B provided convenient observation for locating gene vectors during the transfection processes. This present work provides new useful information for the design of multifunctional gene delivery systems.
Co-reporter:Hao Hu, Hai-Qing Song, Bing-Ran Yu, Qing Cai, Yun Zhu and Fu-Jian Xu
Polymer Chemistry 2015 vol. 6(Issue 13) pp:2466-2477
Publication Date(Web):30 Jan 2015
DOI:10.1039/C4PY01756K
The development of safe and effective supramolecular polycations has attracted much attention. In this work, a series of novel cyclodextrin (CD)-based supramolecular assemblies were readily prepared via the host–guest interaction by assembling different adamantane-functionalized α-CD derivatives with multiple β-CD-cored polycations. The supramolecular assemblies were investigated in terms of their pDNA-binding capabilities, cytotoxicities, cellular internalization and gene transfection efficiencies in HEK293, HepG2 and C6 cell lines. The supramolecular polycations displayed low cytotoxicities, similar to those of the CD-cored carriers. After self-assemblies, the gene transfection efficiencies and antitumor abilities of the supramolecular carriers were significantly enhanced. The present study demonstrates that such supramolecular preparation of CD-based polycations could provide a flexible strategy for the design and development of new assemblies with high efficiency and low cytotoxicity.
Co-reporter:Hai-Qing Song, Xue-Bo Dou, Rui-Quan Li, Bing-Ran Yu, Na-Na Zhao, Fu-Jian Xu
Acta Biomaterialia 2015 Volume 12() pp:156-165
Publication Date(Web):15 January 2015
DOI:10.1016/j.actbio.2014.10.041
Abstract
Owing to their unique properties such as low cytotoxicity and excellent biocompatibility, poly(aspartic acid) (PAsp) and polysaccharides are good candidates for the development of new biomaterials. In order to construct better gene delivery systems by combining polysaccharides with PAsp, in this work, a general strategy is described for preparing series of polysaccharide-graft-PAsp (including cyclodextrin (CD), dextran (Dex) and chitosan (CS)) gene vectors. Such different polysaccharide-based vectors are compared systematically through a series of experiments including degradability, pDNA condensation capability, cytotoxicity and gene transfection ability. They possess good degradability, which would benefit the release of pDNA from the complexes. They exhibit significantly lower cytotoxicity than the control ‘gold-standard’ polyethylenimine (PEI, ∼25 kDa). More importantly, the gene transfection efficiency of Dex- and CS-based vectors is 12–14-fold higher than CD-based ones. This present study indicates that properly grafting degradable PAsp from polysaccharide backbones is an effective means of producing a new class of degradable biomaterials.
Co-reporter:Xinyi Lin, Nana Zhao, Peng Yan, Hao Hu, Fu-Jian Xu
Acta Biomaterialia 2015 Volume 11() pp:381-392
Publication Date(Web):1 January 2015
DOI:10.1016/j.actbio.2014.09.004
Abstract
Silica nanoparticles are attractive candidates for the development of safe and efficient non-viral gene carriers, owing to their controlled morphologies, potential of facile surface modification and excellent biocompatibility as well as in vivo biodegradability. Conversely, the size and shape of nanoparticles are considered to have an intense influence on their interaction with cells and biological systems, but the effects of particle size and shape on gene transfection are poorly understood. In this work, a series of novel gene carriers were designed employing polycation modified silica nanoparticles with five different morphologies, while keeping uniform zeta potential and surface functionality. Then the effects of particle size and shape of these five different carriers on gene transfection were investigated. The morphology of silica nanoparticles is demonstrated to play an important role in gene transfection, especially when the amount of polycation is low. Chiral nanorods with larger aspect ratio were found to fabricate the most efficient gene carriers with compromised cytotoxicity. It was also noted that hollow nanosphere-based carriers exhibited better gene transfection performance than did solid counterparts. These results may provide new strategies to develop promising gene carriers and useful information for the application of nanoparticles in biomedical areas.
Co-reporter:Ranran Wang;Hao Hu;Qin Cai;Nana Zhao;Yun Zhu;Fujian Xu
Science China Chemistry 2015 Volume 58( Issue 9) pp:1461-1470
Publication Date(Web):2015/09/01
DOI:10.1007/s11426-015-5327-8
Successful gene vectors should be with high transfection efficiency and minimal cytotoxicity. Natural polysaccharides, due to their good biocompatibility and biodegradability, have been widely studied and applied. Amylopectin is one of polysaccharides with dendritic structure and numerous hydroxyl groups that could be used for subsequent modification. In this work, a series of dendritic cationic gene vectors comprising amylopectin backbones and poly(2-(dimethylamino) ethyl methacrylate) (PDMAEMA) side chains with different lengths (termed as AMY-PDs) were readily prepared by atom transfer radical polymerization (ATRP). The gene condensation ability, cytotoxicity and gene transfection of AMY-PDs carriers were investigated. In comparison with “gold-standard” poly(ethyleneimine) (PEI, 25 kDa), the AMY-PDs exhibited higher transfection efficiency with lower cytotoxicity. AMY-PDs could be further modified with Au nanoparticles (termed as AMY-PD@Au). The potential of the AMY-PD@Au vectors to be utilized as a CT contrast agent for imaging of cancer cells was investigated. Such AMY-PD@Au vectors may realize gene therapy with the ability of real-time imaging.
Co-reporter:Yang Hu, Nana Zhao, Bingran Yu, Fusheng Liu and Fu-Jian Xu
Nanoscale 2014 vol. 6(Issue 13) pp:7560-7569
Publication Date(Web):06 May 2014
DOI:10.1039/C4NR01590H
Different polysaccharide-based supramolecular polycations were readily synthesized by assembling multiple β-cyclodextrin-cored star polycations with an adamantane-functionalized dextran via host–guest interaction in the absence or presence of bioreducible linkages. Compared with nanoplexes of the starting star polycation and pDNA, the supramolecular polycation/pDNA nanoplexes exhibited similarly low cytotoxicity, improved cellular internalization and significantly higher gene transfection efficiencies. The incorporation of disulfide linkages imparted the supramolecular polycation/pDNA nanoplexes with the advantage of intracellular bioreducibility, resulting in better gene delivery properties. In addition, the antitumor properties of supramolecular polycation/pDNA nanoplexes were also investigated using a suicide gene therapy system. The present study demonstrates that the proper assembly of cyclodextrin-cored polycations with adamantane-functionalized polysaccharides is an effective strategy for the production of new nanoplex delivery systems.
Co-reporter:Xinchao Yang, Nana Zhao and Fu-Jian Xu
Nanoscale 2014 vol. 6(Issue 11) pp:6141-6150
Publication Date(Web):02 Apr 2014
DOI:10.1039/C4NR00907J
Graphene oxide (GO) has been proven to be promising in many biomedical fields due to its biocompatibility, unique conjugated structure, easily tunable surface functionalization and facile synthesis. In this work, a flexible two-step method was first developed to introduce the atom transfer radical polymerization (ATRP) initiation sites containing disulfide bonds onto GO surfaces. Surface-initiated ATRP of (2-dimethyl amino)ethyl methacrylate (DMAEMA) was then employed to tailor the GO surfaces in a well-controlled manner, producing a series of organic–inorganic hybrids (termed as SS–GPDs) for highly efficient gene delivery. Under reducible conditions, the PDMAEMA side chains can be readily cleavable from the GO backbones, benefiting the resultant gene delivery process. Moreover, due to the conjugated structure of the graphene basal plane, SS–GPD can attach and absorb aromatic, water insoluble drugs, such as 10-hydroxycamptothecin (CPT), producing SS–GPD–CPT. The MTT assay and the simultaneous double-staining procedure revealed that SS–GPD–CPT possessed a high potency of killing cancer cells in vitro. With a high aqueous solubility and coulombic interaction with cell membrane, SS–GPDs may have great potential in gene/drug delivery fields.
Co-reporter:Yan-Yu Yang, Xing Wang, Yang Hu, Hao Hu, De-Cheng Wu, and Fu-Jian Xu
ACS Applied Materials & Interfaces 2014 Volume 6(Issue 2) pp:1044
Publication Date(Web):December 3, 2013
DOI:10.1021/am404585d
The bioreducible star-shaped gene vector (POSS-(SS-PDMAEMA)8) with well-defined structure and relatively narrow molecular weight distribution was synthesized via atom transfer radical polymerization (ATRP) of (2-dimethylamino)ethyl methacrylate (DMAEMA) from a polyhedral oligomeric silsesquioxane (POSS) macroinitiator. POSS-(SS-PDMAEMA)8 was composed of a biocompatible POSS core and eight disulfide-linked PDMAEMA arms, wherein the PDMAEMA chain length could be adjusted by controlling polymerization time. POSS-(SS-PDMAEMA)8 can effectively bind pDNA into uniform nanocomplexes with appropriate particle size and zeta potential. The incorporation of disulfide bridges gave the POSS-(SS-PDMAEMA)8 material facile bioreducibility. In comparison with POSS-(PDMAEMA)8 without disulfide linkage, POSS-(SS-PDMAEMA)8 exhibited much lower cytotoxicity and substantially higher transfection efficiency. The present work would provide useful information for the design of new POSS-based drug/gene carriers.Keywords: bioreducible; disulfide bond; gene transfection; POSS; vector;
Co-reporter:Yu Zhao, Bingran Yu, Hao Hu, Yang Hu, Na-Na Zhao, and Fu-Jian Xu
ACS Applied Materials & Interfaces 2014 Volume 6(Issue 20) pp:17911
Publication Date(Web):September 23, 2014
DOI:10.1021/am5046179
The development of new cationic nanoparticles that are safe and effective for biomedical applications has attracted considerable attention. Low molecular weight polycations generally exhibit low toxicity; however, their poor efficiency in drug delivery systems hampers their application. In this work, a series of new low molecular weight 2,6-bis(1-methylbenzimidazolyl)pyridinyl (BIP)-terminated ethanolamine-functionalized poly(glycidyl methacrylate)s (BIP-PGEAs) were readily fabricated for effective codelivery of a gene and a drug. The BIP-PGEAs could form well-defined cationic nanoparticles (NPs) in an aqueous solution. They could effectively bind pDNA with an appropriate particle size and ζ-potential. More importantly, the BIP-PGEA NPs demonstrated much higher transfection efficiencies than linear PGEA (L-PGEA) and the traditional “gold-standard” branched polyethylenimine (25 kDa). Moreover, the BIP-PGEA NPs could effectively entrap a hydrophobic anticancer drug such as 10-hydroxy camptothecin (CPT). The synergistic antitumor effect of the BIP-PGEA-CPT NPs was demonstrated by employing a suicide gene therapy system, which contained cytosine deaminase and 5-fluorocytosine (CD/5-FC). The present strategy for preparing well-defined cationic nanoparticles from low-molecular-weight polycations could provide an intriguing method to produce new multifunctional, therapeutic NPs.Keywords: amphiphilic polymers; ATRP; delivery; gene vector; nanoparticles
Co-reporter:R. Q. Li, Y. L. Niu, N. N. Zhao, B. R. Yu, C. Mao, and F. J. Xu
ACS Applied Materials & Interfaces 2014 Volume 6(Issue 6) pp:3969
Publication Date(Web):March 2, 2014
DOI:10.1021/am5005255
The development of safe and effective β-cyclodextrin (β-CD)-cored cationic star gene carriers has attracted considerable attention. In this work, a series of star-shaped hemocompatible CD-PGPP, CD-PGAEPP, and CD-PGAPP vectors composed of β-CD cores and piperazine (PP)-, N-(aminoethyl)piperazine (AEPP)-, or N-(3-aminopropyl)-2-pyrrolidinone (APP)-functionalized poly(glycidyl methacrylate) arms were successfully proposed and compared for highly efficient gene delivery. Such star carriers possess plentiful secondary amine, tertiary amine, and nonionic hydroxyl groups. CD-PGPP, CD-PGAEPP, and CD-PGAPP were effective in condensing plasmid DNA into nanoparticles, whose sizes were 100–200 nm and positive ζ potentials were 25–40 mV at nitrogen/phosphate (N/P) ratios of 10 and above. CD-PGPP, CD-PGAEPP, and CD-PGAPP showed significantly lower cytotoxicity than control poly(ethylenimine) (PEI; ∼25 kDa). At most N/P ratios, CD-PGAPP exhibited better gene transfection performance than CD-PGPP and CD-PGAEPP particularly in HepG2 cells. More importantly, in comparison with PEI, all of the CD-PGPP, CD-PGAEPP, and CD-PGAPP vectors did not cause undesirable hemolysis.Keywords: gene delivery; piperazine; pyrrolidinone; star vector; β-cyclodextrin;
Co-reporter:Peng Yan, Nana Zhao, Hao Hu, Xinyi Lin, Fusheng Liu, Fu-Jian Xu
Acta Biomaterialia 2014 Volume 10(Issue 8) pp:3786-3794
Publication Date(Web):August 2014
DOI:10.1016/j.actbio.2014.05.002
Abstract
The fabrication of highly efficient nonviral gene carriers with low cytotoxicity remains a challenge in gene therapy. This paper reports a facile strategy to combine the advantages of gold nanorods (Au NRs) and polycations through surface functionalization. Different Au NR carriers with a controlled amount of poly(2-(N,N-dimethyl amino)ethyl methacrylate) (PDAEMA) brushes could be readily synthesized via surface-initiated atom transfer radical polymerization to achieve optimized nanohybrids for gene transfection. The obtained gene carriers demonstrate much higher gene transfection efficiency and lower cytotoxicity compared with polyethylenimine (∼25 kDa, gold standard of nonviral gene vector) in both COS7 and HepG2 cell lines. In addition, the potential of the PDMAEMA-grafted Au NR carriers to be utilized as a computed tomography contrast agent for the imaging of cancer cells has also been investigated. This strategy may realize the gene therapy and real-time imaging within one nanostructure and facilitate biomedical applications.
Co-reporter:R. Q. Li, Y. Hu, B. R. Yu, N. N. Zhao, and F. J. Xu
Bioconjugate Chemistry 2014 Volume 25(Issue 1) pp:155
Publication Date(Web):December 11, 2013
DOI:10.1021/bc400467h
Comb-shaped polymeric vectors (SS-PGEADMs) consisting of ethanolamine/cystamine-functionalized poly(glycidyl methacrylate) (SS-PGEA-NH2) backbones and bioreducible poly((2-dimethyl amino)ethyl methacrylate) (PDMEAMA) side chains were prepared by a combination of the ring-opening reaction and atom transfer radical polymerization (ATRP). The SS-PGEA-NH2 backbones, which were prepared via the ring-opening reaction of the pendant epoxide groups of poly(glycidyl methacrylate) with the amine moieties of ethanolamine/cystamine, possess plentiful flanking secondary amine and hydroxyl groups and some flanking disulfide bond-containing cystamine derivatives. The primary amine groups of the cystamine derivatives were activated to produce bromoisobutylryl-terminated SS-PGEA (SS-PGEA-Br) as multifunctional initiators for subsequent ATRP of DMAEMA. The resultant disulfide-linked short PDMEAMA side chains possess pendant tertiary amine groups and are biocleavable. Such SS-PGEADMs can effectively condense pDNA. The cytotoxicity of SS-PGEADMs could be controlled by adjusting the grafting amount of PDMEAMA side chains. In comparison with the pristine SS-PGEA-NH2, the moderate introduction of PDMEAMA side chains can further enhance the gene transfection efficiency in different cell lines. The present approach to well-defined comb-shaped vectors with multifunctional groups could provide a versatile means for tailoring the functional structures of advanced gene/drug vectors.
Co-reporter:Yun Zhu;Xuefeng Zheng;Bingran Yu;Wantai Yang;Nana Zhao;Fujian Xu
Macromolecular Bioscience 2014 Volume 14( Issue 8) pp:1135-1148
Publication Date(Web):
DOI:10.1002/mabi.201400062
In this work, a simple one-step method is first employed to produce the bromoisobutyryl-terminated 2-hydroxypropyl-β-cyclodextrin (HPCD-Br). The pendant epoxy groups of poly(glycidyl methacrylate) block prepared via ATRP from HPCD-Br can be reacted with ethanolamine to produce HPCD-PGEA which exhibits much lower cytotoxicity and better gene transfection yield than polyethylenimine (25 kDa) in COS7 and HepG2 cell lines. Moreover, poly((2-dimethyl amino)ethyl methacrylate) blocks can be incorporated into low-molecular-weight HPCD-PGEA via “click” reaction to further enhance the gene transfection efficiency in HepG2 cell lines.
Co-reporter:Wei Yuan;NaNa Zhao;BingRan Yu;Hui Jiang;Jie Ma;FuJian Xu
Science China Chemistry 2014 Volume 57( Issue 4) pp:586-595
Publication Date(Web):2014 April
DOI:10.1007/s11426-013-5028-0
Efficient local gene transfection on a tissue scaffold is dependent on good cell-adhesion characteristics. In this work, the thermo-responsive gelatin-functionalized polycaprolactone (PCL) films were proposed for improvement of cell adhesion and intelligent recovery of gene-transfected cells. Functional copolymer brushes (PCL-g-P(NIPAAm-co-MAAS)) were first prepared via surface-initiated ATRP of N-isopropylacrylamide (NIPAAm) and methacrylic acid sodium salt (MAAS) from the initiator-funcationalized PCL surfaces. The pendant carboxyl end-groups of the PCL-g-P(NIPAAm-co-MAAS) surface were subsequently coupled with gelatin via carbodiimide chemistry to produce the thermo-responsive gelatin-functionalized PCL surface. The thermo-responsive gelatin-functionalized PCL film surface can improve cell adhesion and proliferation above the LCST of P(NIPAAm) without destroying cell detachment properties at lower temperatures. The dense transfected cells can be recovered simply by lowering culture temperature. The thermo-responsive gelatin-functionalized PCL films are potentially useful as intelligent adhesion modifiers for directing cellular functions within tissue scaffolds.
Co-reporter:X.B. Dou, Y. Hu, N.N. Zhao, F.J. Xu
Biomaterials 2014 35(9) pp: 3015-3026
Publication Date(Web):
DOI:10.1016/j.biomaterials.2013.12.017
Co-reporter:Hui Jiang and Fu-Jian Xu
Chemical Society Reviews 2013 vol. 42(Issue 8) pp:3394-3426
Publication Date(Web):24 Jan 2013
DOI:10.1039/C2CS35453E
Functional polymer brushes have been utilized extensively for the immobilization of biomolecules, which is of crucial importance for the development of biosensors and biotechnology. Recent progress in polymerization methods, in particular surface-initiated atom transfer radical polymerization (ATRP), has provided a unique means for the design and synthesis of new biomolecule-functionalized polymer brushes. This current review summarizes such recent research activities. The different preparation strategies for biomolecule immobilization through polymer brush spacers are described in detail. The functional groups of the polymer brushes used for biomolecule immobilization include epoxide, carboxylic acid, hydroxyl, aldehyde, and amine groups. The recent research activities indicate that functional polymer brushes become versatile and powerful spacers for immobilization of various biomolecules to maximize their functionalities. This review also demonstrates that surface-initiated ATRP is used more frequently than other polymerization methods in the designs of new biomolecule-functionalized polymer brushes.
Co-reporter:Y. Hu, Y. Zhu, W.T. Yang, and F. J. Xu
ACS Applied Materials & Interfaces 2013 Volume 5(Issue 3) pp:703
Publication Date(Web):December 27, 2012
DOI:10.1021/am302249x
The biocleavable star-shaped vectors (CD-SS-PGEAs) consisting of nonionic β-cyclodextrin (β-CD) cores and disulfide-linked low-molecular-weight poly(glycidyl methacrylate) (PGMA) derivative arms with plentiful flanking secondary amine and hydroxyl groups were successfully proposed for highly efficient gene delivery. A simple two-step method was first adopted to introduce reduction-sensitive disulfide-linked initiation sites of atom transfer radical polymerization (ATRP) onto β-CD cores. The disulfide-linked PGMA arms prepared subsequently via ATRP were functionalized via the ring-opening reaction with ethanolamine (EA) to produce the cationic EA-functionalized PGMA (PGEA) arms with plentiful secondary amine and nonionic hydroxyl units. The cationic PGEA arms can be readily cleavable from the β-CD cores under reducible conditions. Such biocleavable star-shaped CD-SS-PGEA vectors possessed the good pDNA condensation ability, low cytotoxicity, and efficient gene delivery ability.Keywords: ATRP; bioreducible vector; gene delivery; PGEA; β-cyclodextrin;
Co-reporter:Yun Zhu, Gu-Ping Tang, and Fu-Jian Xu
ACS Applied Materials & Interfaces 2013 Volume 5(Issue 5) pp:1840
Publication Date(Web):February 19, 2013
DOI:10.1021/am400022q
High-molecular-weight comb-shaped cationic copolymers have been of interest and importance as nonviral gene delivery carriers. Poly(dl-aspartamide)-based biomaterials with good degradability and excellent biocompatibility could be used as the potential backbones of gene vectors. In this work, atom transfer radical polymerization (ATRP) was proposed to prepare the biocleavable and biodegradable comb-shaped poly(N-3-hydroxypropyl)aspartamide (PHPA)-based gene carriers. The bioreducible ATRP initiation sites were first introduced onto PHPA backbones. Then, the well-defined comb-shaped vectors (SS-PHPDs) consisting of degradable PHPD backbones and disulfide-linked cationic P(DMAEMA) side chains were produced for gene delivery. The P(DMAEMA) side chains were readily cleavable from the backbones under reducible conditions. The degradability of PHPA backbones would benefit the final removal of the gene carriers from the body.Keywords: ATRP; biodegradable; bioreducible; gene delivery; P(DMAEMA); PHPA;
Co-reporter:X. B. Dou, M. Y. Chai, Y. Zhu, W. T. Yang, and F. J. Xu
ACS Applied Materials & Interfaces 2013 Volume 5(Issue 8) pp:3212
Publication Date(Web):March 20, 2013
DOI:10.1021/am4002277
Aminated poly(glycidyl methacrylate) (PGMA) vectors could efficiently mediate gene delivery. Recently, we reported that ethanolamine (EA)-functionalized PGMA could provide high transfection efficiency, while exhibiting very low toxicity. Herein, different amine species, including 1-amino-2-propanol (AP1), 3-amino-2-propanol (AP2), EA, and N,N,-dimethylethylenediamine (DED), and its quaternized DED, were proposed to aminate PGMA. The DNA condensation abilities, pH buffering capacities, cytotoxicities, and gene transfection efficiencies of the resultant aminated PGMA vectors were systematically compared. Compared with EA, AP1 (or AP2) contains an additional methyl (or methylene) group. EA-, AP1-, and AP2-functionalized PGMA vectors exhibited similar condensation abilities. The methyl (from AP1) and methylene (from AP2) species could benefit the gene delivery. The transfection performance mediated by AP1-functionalized PGMA is best. DED possesses a tertiary amine group, which could be quaternized to further enhance the DNA condensation ability of aminated PGMA. No obvious increase in cytotoxicity of quaternized DED-aminated PGMA was observed. But both DED- and its quaternized counterpart-functionalized PGMA vectors exhibited very low pH buffering capacities, making them exhibit poor gene transfection performances. The current study would provide useful information for constructing better PGMA-based delivery systems with good biophysical properties.Keywords: 1-amino-2-propanol; 3-amino-2-propanol; ethanolamine; gene delivery; GMA; N,N,-dimethylethylenediamine;
Co-reporter:Ke-Mao Xiu, Na-Na Zhao, Wan-Tai Yang, Fu-Jian Xu
Acta Biomaterialia 2013 Volume 9(Issue 7) pp:7439-7448
Publication Date(Web):July 2013
DOI:10.1016/j.actbio.2013.04.010
Abstract
For ideal polymeric gene vectors, their serum stability is of crucial importance. Polycation vectors usually suffer from colloidal aggregation, which makes them easily cleared from the bloodstream. Recently, we reported a comb-shaped vector (DPD) consisting of a dextran backbone and disulfide-linked cationic poly((2-dimethyl amino)ethyl methacrylate) side chains for efficient gene delivery. In this work, versatile functionalization of DPD (as a model gene vector) was proposed via the introduction of different types of zwitterionic carboxybetaine and sulfobetaine species for improving biophysical properties. The incorporation of zwitterionic betaine did not destroy the DNA condensation capability of vectors. All the zwitterionic betaine-functionalized DPD vectors exhibited lower cytotoxicities than the pristine DPD. The DPD-b-polycarboxybetaine block copolymer (DPDbPC) exhibited better gene delivery abilities than the corresponding DPD-r-polycarboxybetaine random copolymer (DPDrPC). Moreover, in the serum case with a high concentration (30%) of fetal bovine serum, the DPD-b-polysulfobetaine block copolymer (DPDbPS) produced much higher gene transfection efficiencies than DPDbPC. Cellular internalization results indicated that the incorporation of zwitterionic betaine could benefit serum stabilities of vectors and enhance cellular uptake. The present study demonstrated that proper incorporation of zwitterionic betaine into gene carriers was an effective method to produce serum-tolerant transfection vectors.
Co-reporter:K.M. Xiu, J.J. Yang, N.N. Zhao, J.S. Li, F.J. Xu
Acta Biomaterialia 2013 Volume 9(Issue 1) pp:4726-4733
Publication Date(Web):January 2013
DOI:10.1016/j.actbio.2012.08.020
Abstract
Controlled β-cyclodextrin (β-CD) core-based cationic star polymers have attracted considerable attention as non-viral gene carriers. Atom transfer radical polymerization (ATRP) could be readily used to produce the star-shaped polymers. The precise control of the number of initiation sites on the multifunctional core was of crucial importance to the investigation of the structure–property relationship of the functional star gene carriers. Herein, the controlled multiarm star polymers consisting of a β-CD core and various arm lengths of poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) were prepared via ATRP from the chloroacetylated β-CD with well-designed initiation sites. Generally, these star polycations can condense plasmid DNA into 100–150 nm nanoparticles with positive zeta potentials of 30–40 mV at N/P ratios (star polymer to DNA ratios) of 17 or higher. The effects of arm numbers and lengths on gene delivery were investigated in detail. With a fixed length of the PDMAEMA arm, the fewer the number of arms, the lower the toxicity. The star polycations with suitable arm numbers possess the best transfection ability. On the other hand, with the fixed molecular weights, the shorter the arms, the lower the toxicity. The polymers with 21 arms possess the lowest transfection efficiency.
Co-reporter:Y. Hu, M. Y. Chai, W. T. Yang, and F. J. Xu
Bioconjugate Chemistry 2013 Volume 24(Issue 6) pp:1049
Publication Date(Web):May 20, 2013
DOI:10.1021/bc400115e
A series of novel supramolecular pseudocomb polycations (l-PGEA-Ad/CD-PGEAs) were synthesized by tying multiple low-molecular-weight β-cyclodextrin (CD)-cored, ethanolamine-functionalized poly(glycidyl methacrylate) (PGEA) star polymers (CD-PGEAs) with an adamantine-modified linear PGEA (l-PGEA-Ad) backbone via the host–guest interaction. The pseudocomb carriers were studied in terms of their DNA binding capabilities, cytotoxicities, and gene transfection efficiencies in the HepG2 and HEK293 cell lines. The pseudocomb l-PGEA-Ad/CD-PGEAs exhibited better plasmid DNA-condensing abilities than their counterparts, CD-PGEA and l-PGEA. Meanwhile, the pseudocomb carriers displayed low cytotoxicity, similar to CD-PGEA and l-PGEA. Moreover, the gene transfection efficiencies of the pseudocomb carriers were much higher than those of CD-PGEA and l-PGEA at various PGEA nitrogen/DNA phosphate molar ratios. Such supramolecular preparation of pseudocomb gene carriers could provide a flexible approach for adjusting the structure and functionality of supramolecular polymers via the proper use of non-covalent interactions.
Co-reporter:H. Hu, K. M. Xiu, S. L. Xu, W. T. Yang, and F. J. Xu
Bioconjugate Chemistry 2013 Volume 24(Issue 6) pp:968
Publication Date(Web):May 20, 2013
DOI:10.1021/bc300683y
Layered double hydroxides (LDHs) have aroused great attention as potential nanosized drug delivery carriers, but independent inorganic LDH wrapped with DNA shows very low transfection efficiency. To manipulate and control the surface properties of LDH nanoparticles is of crucial importance in the designing of LDH-based drug carriers. In this work, surface-initiated atom transfer radical polymerization (ATRP) of 2-(dimethylamino)ethyl methacrylate (DMAEMA) is employed to tailor the functionality of LDH surfaces in a well-controlled manner and produce a series of well-defined novel gene delivery vectors (termed as LDH-PDs), where a flexible three-step method was first developed to introduce the ATRP initiation sites containing disulfide bonds onto LDH surfaces. In comparison the pristine LDH particles, the resultant LDH-PDs exhibited better ability to condense plasmid DNA (pDNA) and much higher levels to delivery genes in different cell lines including COS7 and HepG2 cell lines. Moreover, the LDH-PDs also could largely enhance cellular uptake. This present study demonstrates that functionalization of bioinorganic LDH with flexible polycation brushes is an effective means to produce new LDH-based gene delivery systems.
Co-reporter:Yang Hu, Wei Yuan, Na-Na Zhao, Jie Ma, Wan-Tai Yang, Fu-Jian Xu
Biomaterials 2013 34(21) pp: 5411-5422
Publication Date(Web):
DOI:10.1016/j.biomaterials.2013.03.092
Co-reporter:J. Shen, D.J. Zhao, W. Li, Q.L. Hu, Q.W. Wang, F.J. Xu, G.P. Tang
Biomaterials 2013 34(18) pp: 4520-4531
Publication Date(Web):
DOI:10.1016/j.biomaterials.2013.02.068
Co-reporter:Y. Hu, J.S. Li, W.T. Yang, F.J. Xu
Thin Solid Films 2013 Volume 534() pp:325-333
Publication Date(Web):1 May 2013
DOI:10.1016/j.tsf.2013.02.020
The ability to manipulate and control the surface properties of polymer films, without altering the substrate properties, is crucial to their wide-spread applications. In this work, a simple one-step method for the direct immobilization of benzyl chloride groups (as the effective atom transfer radical polymerization (ATRP) initiators) on the polymer films was developed via benzophenone-induced coupling of 4-vinylbenzyl chloride (VBC). Polyethylene (PE) and nylon films were selected as examples of polymer films to illustrate the functionalization of film surfaces via surface-initiated ATRP. Functional polymer brushes of (2-dimethylamino)ethyl methacrylate, sodium 4-styrenesulfonate, 2-hydroxyethyl methacrylate and glycidyl methacrylate, as well as their block copolymer brushes, have been prepared via surface-initiated ATRP from the VBC-coupled PE or nylon film surfaces. With the development of a simple approach to the covalent immobilization of ATRP initiators on polymer film surfaces and the inherent versatility of surface-initiated ATRP, the surface functionality of polymer films can be precisely tailored.Highlights► Atom transfer radical polymerization initiators were simply immobilized. ► Different functional polymer brushes were readily prepared. ► Their block copolymer brushes were also readily prepared.
Co-reporter:Wei Yuan;Chunyan Li;Chen Zhao;Chenguang Sui;Wan-Tai Yang;Jie Ma
Advanced Functional Materials 2012 Volume 22( Issue 9) pp:1835-1842
Publication Date(Web):
DOI:10.1002/adfm.201102221
Abstract
Efficient local gene transfection on a tissue scaffold is of crucial importance in facilitating tissue repair and regeneration. In this work, the gelatin-functionalized polycaprolactone (PCL) film surfaces are prepared via surface-initiated atom transfer radical polymerization of glycidyl methacrylate. The resultant covalent attachment of gelatin could enhance the cell-adhesion and local gene transfection properties. The gelatin-functionalized PCL film surfaces exhibit excellent cell-adhesion ability to both adherent and suspension cells. The attached adherent cells demonstrate the characteristic elongated morphologies with good spreading capability, while the attached suspension cells can maintain the original status of the round morphologies without spreading. More importantly, the gelatin coupled on the PCL surface could be used to absorb the cationic vector/plasmid deoxyribonucleic acid (pDNA) complexes via electrostatic interaction. The local gene transfection property on the immobilized cells is dependent on both the density of the immobilized cells and the loading types of pDNA complexes. The transfection efficiency of different assemble methods of pDNA complex was compared. With the pre- and post-loading sandwich-like gene transfection, the gelatin-functionalized PCL film surface can substantially enhance the transfection properties to different cell lines. The present study is very useful to spatially control local gene delivery within PCL-based tissue scaffolds.
Co-reporter:Y. Hu, N. N. Zhao, J. S. Li, W. T. Yang and F. J. Xu
Journal of Materials Chemistry A 2012 vol. 22(Issue 39) pp:21257-21264
Publication Date(Web):28 Aug 2012
DOI:10.1039/C2JM34919A
The inherent hydroxyl groups on the porous polycaprolactone (PPCL) films (prepared by using poly(ethylene glycol) as the pore-forming agent) could be reacted with 2-bromoisobutyrate bromide to produce a sufficient concentration of surface-coupled atom transfer radical polymerization (ATRP) initiators for the subsequent surface-initiated ATRP of thermo-responsive N-isopropylacrylamide (NIPAAm) at room temperature. A kinetics study revealed that the chain growth of the grafted NIPAAm polymer (P(NIPAAm)) was very fast and consistent with a ‘controlled’ process. The graft copolymerization not only occurred on the porous film surface, but also took place into the film bulk. The resultant P(NIPAAm)-grafted PPCL (PPCL-g-P(NIPAAm)) films assumed a uniform and interconnected porous structure and exhibited a temperature-sensitive property with a lower critical solution temperature (LCST) of about 32 °C, not unlike pure P(NIPAAm). The release of bovine serum albumin (BSA as a model protein) from the PPCL-g-P(NIPAAm) films was characterized by an initial burst, followed by a sustained release. These thermo-responsive PPCL-g-P(NIPAAm) porous films are potentially useful in biomedical fields.
Co-reporter:H. Hu, X. B. Wang, S. L. Xu, W. T. Yang, F. J. Xu, J. Shen and C. Mao
Journal of Materials Chemistry A 2012 vol. 22(Issue 30) pp:15362-15369
Publication Date(Web):07 Jun 2012
DOI:10.1039/C2JM32720A
The ability to manipulate and control the surface properties of layered double hydroxide (LDH) nanoparticles is of crucial importance in the designing of LDH-based carriers of therapeutic agents. In this work, surface-initiated atom transfer radical polymerization (ATRP) of zwitterionic 3-dimethyl(methacryloyloxyethyl) ammonium propane sulfonate (DMAPS) is first employed to tailor the functionality of LDH surfaces in a well-controlled manner and produce a series of well-defined hemocompatible hybrids (termed as LDHPS). The blood compatibilities of the modified LDH nanoparticles were investigated using coagulation tests, complement activation, platelet activation, hemolysis assay, morphological changes of red blood cells, and cytotoxicity assay. The results confirmed that the P(DMAPS) grafting can substantially enhance the hemocompatibility of the LDH particles, and the LDHPS hybrids can be used as biomaterials without causing any hemolysis. With the versatility of surface-initiated ATRP and the excellent hemocompatibility of zwitterionic polymer chains, the LDH nanoparticles with desirable blood properties can be readily tailored to cater to various biomedical applications.
Co-reporter:Q. Cai, Y. Zhu, J. Q. He, Z. H. Wang, Fabing Su, F. J. Xu, X. P. Yang and W. T. Yang
Journal of Materials Chemistry A 2012 vol. 22(Issue 18) pp:9358-9367
Publication Date(Web):15 Mar 2012
DOI:10.1039/C2JM31109G
The ability to manipulate and control the surface properties of hydroxyapatite (HA) nanoparticles is of crucial importance for the design of HA-based carriers of therapeutic agents. In this work, surface-initiated atom transfer radical polymerization (ATRP) of (2-dimethyl amino)ethyl methacrylate (DMAEMA) is first employed to tailor the functionality of HA surfaces in a well-controlled manner and to produce a series of new cationic hybrids (termed as HA-PDM). The HA parts of HA-PDM were coated by different lengths of PDMAEMA chains. The HA-PDM exhibited a good ability to condense plasmid DNA (pDNA) with suitable particle size and a zeta potential for gene transfection. Most importantly, in comparison with PDMAEMA homopolymers, the HA-PDM displayed considerably enhanced buffering capacity, and exhibited much higher gene transfection efficiencies in different cell lines, including osteoblast MC3T3 and osteosarcoma MG63 cells. In addition, the HA-PDM/pDNA complexes also could largely enhance the differentiation of preosteoblast cells. Such well-defined HA-PDM nanohybrids possess great potential applications as new drug-delivery vectors in bone tissue engineering.
Co-reporter:X. C. Yang, M. Y. Chai, Y. Zhu, W. T. Yang and F. J. Xu
Journal of Materials Chemistry A 2012 vol. 22(Issue 16) pp:7806-7812
Publication Date(Web):12 Mar 2012
DOI:10.1039/C2JM16166D
It was of crucial importance to modify perylene-3,4,9,10-tetracarboxylic acid bisimides (PBIs) for the design of new perylene-based bio-dye agents with strong fluorescence. Recently, we reported that ethanolamine (EA)-functionalized poly(glycidyl methacrylate) (or PGEA) can produce good transfection efficiency, while exhibiting very low toxicity. Herein, the low-toxic PGEA was proposed to be conjugated with PBIs via facile atom transfer radical polymerization for the well-defined highly fluorescent cationic bifunctional conjugate (PBI–PGEA). The obtained PBI–PGEA exhibited good water-solubility properties, characteristic spectroscopic patterns of PBIs, and excellent photostability. The PBI–PGEA conjugate can be used as an efficient cell bio-dye for rapid (2–5 min) cell labeling at low concentrations (0.06–0.12 mg mL−1). Such a fast labeling process did not induce obvious cytotoxicity, avoiding possible side-effects to the cells. In addition, the PBI–PGEA still possessed good gene transfection efficiency in different cell lines. With the strong fluorescence in water and good transfection properties, the developed bifunctional PBI–PGEA should possess more potential in bioimaging and gene delivery.
Co-reporter:X. C. Yang, M. Y. Chai, Y. Zhu, W. T. Yang, and F. J. Xu
Bioconjugate Chemistry 2012 Volume 23(Issue 3) pp:618
Publication Date(Web):February 14, 2012
DOI:10.1021/bc200658r
Recently, we reported that ethanolamine (EA)-functionalized poly(glycidyl methacrylate) (PGMA) vectors (PGEAs) can produce good transfection efficiency, while exhibiting very low toxicity. Further improvement in degradability and transfection efficiency of the PGEA vectors will facilitate their application in gene therapy. Comb-shaped cationic copolymers have been of interest and importance as nonviral gene carriers. Herein, the degradable high-molecular-weight comb-shaped PGEA vectors (c-PGEAs) composed of the low-molecular-weight PGEA backbone and side chains were prepared by a combination of atom transfer radical polymerization (ATRP) and ring-opening reactions. The PGEA side chains were linked with the PGEA backbones via hydrolyzable ester bonds. Such comb-shaped c-PGEA vectors possessed the degradability, good pDNA condensation ability, low cytotoxicity, and good buffering capacity. More importantly, the comb-shaped c-PGEA vectors could enhance the gene expression levels. Moreover, the PGEA side chains of c-PGEA could also be copolymerized with some poly(poly(ethylene glycol)ethyl ether methacrylate) species to further improve the gene delivery system.
Co-reporter:Hui Fan, Qi-Da Hu, Fu-Jian Xu, Wen-Quan Liang, Gu-Ping Tang, Wan-Tai Yang
Biomaterials 2012 33(5) pp: 1428-1436
Publication Date(Web):
DOI:10.1016/j.biomaterials.2011.10.043
Co-reporter:K.M. Xiu, Q. Cai, J.S. Li, X.P. Yang, W.T. Yang, F.J. Xu
Colloids and Surfaces B: Biointerfaces 2012 90() pp: 177-183
Publication Date(Web):
DOI:10.1016/j.colsurfb.2011.10.023
Co-reporter:Zeng-Hui Wang, Yun Zhu, Ming-Ying Chai, Wan-Tai Yang, Fu-Jian Xu
Biomaterials 2012 33(6) pp: 1873-1883
Publication Date(Web):
DOI:10.1016/j.biomaterials.2011.11.027
Co-reporter:M. Liu, Z.H. Li, F.J. Xu, L.H. Lai, Q.Q. Wang, G.P. Tang, W.T. Yang
Biomaterials 2012 33(7) pp: 2240-2250
Publication Date(Web):
DOI:10.1016/j.biomaterials.2011.11.082
Co-reporter:J.L. Wang, G.P. Tang, J. Shen, Q.L. Hu, F.J. Xu, Q.Q. Wang, Z.H. Li, W.T. Yang
Biomaterials 2012 33(18) pp: 4597-4607
Publication Date(Web):
DOI:10.1016/j.biomaterials.2012.02.045
Co-reporter:F.J. Xu, W.T. Yang
Progress in Polymer Science 2011 Volume 36(Issue 9) pp:1099-1131
Publication Date(Web):September 2011
DOI:10.1016/j.progpolymsci.2010.11.005
The design of efficient gene delivery vectors is a challenging task in gene therapy. Recent progress in living/controlled radical polymerizations (LRPs), in particular atom transfer radical polymerization (ATRP) and reversible addition-fragmentation chain transfer (RAFT) polymerization providing a means for the design and synthesis of new polymeric gene vectors with well-defined compositions, architectures and functionalities is reviewed here. Polymeric gene vectors with different architectures, including homopolymers, block copolymers, graft copolymers, and star-shaped polymers, are conveniently prepared via ATRP and RAFT polymerization. The corresponding synthesis strategies are described in detail. The recent research activities indicate that ATRP and RAFT polymerization have become essential tools for the design and synthesis of advanced, noble and novel gene carriers.
Co-reporter:Yuan Ping;Cheng-De Liu;Gu-Ping Tang;Jian-Shu Li;Jun Li;Wan-Tai Yang
Advanced Functional Materials 2011 Volume 21( Issue 12) pp:
Publication Date(Web):
DOI:10.1002/adfm.201190046
No abstract is available for this article.
Co-reporter:F.J. Xu, Y. Zhu, M.Y. Chai, F.S. Liu
Acta Biomaterialia 2011 Volume 7(Issue 8) pp:3131-3140
Publication Date(Web):August 2011
DOI:10.1016/j.actbio.2011.04.023
Abstract
Cationic polymers with low cytotoxicity and high transfection efficiency have attracted considerable attention as non-viral carriers for gene delivery. Recently we reported that ethanolamine (EA)-functionalized poly(glycidyl methacrylate) (PGMA) (termed PGEA) vectors can have excellent transfection efficiency, while exhibiting very low toxicity. Herein different EA- and ethylenediamine (ED)-functionalized PGMA (termed PGEAED) vectors, as well as ED-functionalized PGMA (termed PGED) vectors, are proposed and compared for efficient gene delivery. In addition to the cationic pendant secondary amine and hydroxyl groups of PGEA, PGEAED, and PGED also contain flanking primary amine groups. PGEAED and PGED exhibited a substantially enhanced ability to condense pDNA into complex nanoparticles at the 100 nm level with positive zeta potentials of about 30 mV at nitrogen/phosphate (N/P) ratios of 10 or higher. More interestingly, no obvious change in the cytotoxicity of PGEAED was observed with a substantial increase in ED content. Moreover, the flanking primary amine groups induced by ED could be readily functionalized by glycyrrhetinic acid or cholic acid to improve the biophysical properties of the gene vectors.
Co-reporter:C. Y. Li, W. Yuan, H. Jiang, J. S. Li, F. J. Xu, W. T. Yang, and J. Ma
Bioconjugate Chemistry 2011 22(9) pp: 1842-1851
Publication Date(Web):August 18, 2011
DOI:10.1021/bc200241m
Successful gene transfection on a tissue scaffold is of crucial importance in facilitating tissue repair and regeneration by enabling the localized production of therapeutic drugs. Polycaprolactone (PCL) has been widely adopted as a scaffold biomaterial, but its unfavorable cell-adhesion property needs to be improved. In this work, the PCL film surface was conjugated with poly((2-dimethyl amino)ethyl methacrylate) (P(DMAEMA))/gelatin complexes via surface-initiated atom transfer radical polymerization (ATRP) for improving cell immobilization and subsequent gene transfection. A simple aminolysis-based method was first used for the covalent immobilization of ATRP initiators on the PCL film. Well-defined P(DMAEMA) brushes were subsequently prepared via surface-initiated ATRP from the initiator-functionalized PCL surfaces. The P(DMAEMA) chains with a pKa of 7.0–7.3 were used for conjugating gelatin with a pI of 4.7 via electrostatic interaction. The amount of complexed gelatin increased as that of the grafted P(DMAEMA) layer. The cell-adhesion property on the functionalized PCL surface could be controlled by adjusting the ratio of P(DMAEMA)/gelatin. It was found that the gene transfection property on the immobilized cells was dependent on the density of the immobilized cells on the functionalized PCL film. With the good cell-adhesive nature of gelatin and the efficient gene transfection on the dense immobilized cells, the incorporating the suitable of P(DMAEMA)/gelatin complexes onto PCL surfaces could endow the PCL substrates new and interesting properties for potential tissue engineering applications.
Co-reporter:Qiying Jiang;Peihua Shi;Chunyan Li;Qingqing Wang;Fujian Xu;Wantai Yang;Guping Tang
Macromolecular Bioscience 2011 Volume 11( Issue 3) pp:435-444
Publication Date(Web):
DOI:10.1002/mabi.201000350
Co-reporter:F. J. Xu, X. C. Yang, C. Y. Li, and W. T. Yang
Macromolecules 2011 Volume 44(Issue 7) pp:2371-2377
Publication Date(Web):March 11, 2011
DOI:10.1021/ma200160h
Co-reporter:H. Jiang, X. B. Wang, C. Y. Li, J. S. Li, F. J. Xu, C. Mao, W. T. Yang, and J. Shen
Langmuir 2011 Volume 27(Issue 18) pp:11575-11581
Publication Date(Web):August 18, 2011
DOI:10.1021/la202101q
Polycaprolactone (PCL) has been widely adopted as a scaffold biomaterial, but further improvement of the hemocompatibility of a PCL film surface is still needed for wide biomedical applications. In this work, the PCL film surface was functionalized with zwitterionic poly(3-dimethyl(methacryloyloxyethyl) ammonium propane sulfonate) (P(DMAPS)) brushes via surface-initiated atom transfer radical polymerization (ATRP) for enhancing hemocompatibility. Kinetics study revealed an approximately linear increase in graft yield of the functional P(DMAPS) brushes with polymerization time. The blood compatibilities of the modified PCL film surfaces were studied by platelet adhesion tests of platelet-rich plasma and human whole blood, hemolysis assay, and plasma recalcification time (PRT) assay. The improvement of hemocompatibility is dependent on the coverage of the grafted P(DMAPS) brushes on the PCL film. Lower or no platelet and blood cell adhesion was observed on the P(DMAPS)-grafted film surfaces. The P(DMAPS) grafting can further decrease hemolysis and enhance the PRT of the PCL surface. With the versatility of surface-initiated ATRP and the excellent hemocompatibility of zwitterionic polymer brushes, PCL films with desirable blood properties can be readily tailored to cater to various biomedical applications.
Co-reporter:F.J. Xu, Y.Q. Zheng, W.J. Zhen, W.T. Yang
Colloids and Surfaces B: Biointerfaces 2011 Volume 85(Issue 1) pp:40-47
Publication Date(Web):15 June 2011
DOI:10.1016/j.colsurfb.2010.09.027
Thermoresponsive poly(N-isopropylacrylamide) (P(NIPAAm))-grafted polycaprolactone (PCL) films with a suitable amount of immobilized cell-adhesive collagen were prepared to improve cell adhesion and proliferation above the lower critical solution temperature (LCST, 32 °C) of P(NIPAAm) without destroying cell detachment properties at lower temperatures. Covalently tethered P(NIPAAm) brushes on PCL film surfaces were first prepared via surface-initiated atom transfer radical polymerization (ATRP). The alkyl bromide end groups of the grafted P(NIPAAm) brushes were used in nucleophilic substitution reactions for the direct coupling of collagen to produce the collagen-immobilized thermoresponsive PCL surface. At 37 °C, the cell attachments on the collagen-immobilized thermoresponsive PCL surface were enhanced substantially. The attached cells could be recovered simply by lowering culture temperature. The P(NIPAAm)-grafted PCL films with immobilized collagen are potentially useful as adhesion modifiers for advanced cell culture and tissue engineering applications.Graphical abstractResearch highlights▶ Thermoresponsive PCL films surfaces can be prepared via surface-initiated ATRP. ▶ Collagen-immobilized thermoresponsive PCL surfaces enhance cell adhesion. ▶ Collagen-immobilized thermoresponsive PCL surfaces donot destroy cell detachment properties.
Co-reporter:Xiao Lu, Qing-Qing Wang, Fu-Jian Xu, Gu-Ping Tang, Wan-Tai Yang
Biomaterials 2011 32(21) pp: 4849-4856
Publication Date(Web):
DOI:10.1016/j.biomaterials.2011.03.022
Co-reporter:Z. H. Wang, W. B. Li, J. Ma, G. P. Tang, W. T. Yang, and F. J. Xu
Macromolecules 2011 Volume 44(Issue 2) pp:230-239
Publication Date(Web):December 22, 2010
DOI:10.1021/ma102419e
It is of crucial importance to modify dextran-based polysaccharides in the design of novel biomedical materials. A simple one-step method, involving the reaction of hydroxyl groups of dextran with α-bromoisobutyric acid in the presence of 1,1′-carbonyldiimidazole, was first developed to produce bromoisobutyryl-terminated dextran as multifunctional initiators for subsequent atom transfer radical polymerization (ATRP). Well-defined comb-shaped copolymers (DPDs) composed of nonionic hydrophilic dextran backbones and cationic poly((2-dimethyl amino)ethyl methacrylate) (or P(DMAEMA)) side chains were subsequently prepared via ATRP for nonviral gene delivery. The P(DMAEMA) side chains of DPDs can be further partially quaternized to produce the quaternary ammonium DPDs (QDPDs). DPD and QDPDs can condense pDNA into complex nanoparticles of 100 to 150 nm in sizes. QDPDs exhibit stronger ability to complex pDNA, due to increased surface cationic charges. DPDs can exhibit much lower cytotoxicity and better gene transfection yield than high-molecular-weight P(DMAEMA) homopolymers and “gold-standard” polyethylenimine (25 kDa) in HEK293 and L929 cell lines. DPDs also exhibit efficient gene delivery ability in different cancer cell lines, especially in MCF7 cells where the DPD-mediated transfection efficiency is almost 3 times higher than that of the popular Lipfectamine 2000 transfection reagent. This study demonstrated that grafting low-molecular-weight polymer chains from natural dextran backbones via ATRP is an effective means to produce novel polysaccharide-based nanobiomaterials.
Co-reporter:Qi-Ying Jiang, Li-Hua Lai, Jie Shen, Qing-Qing Wang, Fu-Jian Xu, Gu-Ping Tang
Biomaterials 2011 32(29) pp: 7253-7262
Publication Date(Web):
DOI:10.1016/j.biomaterials.2011.06.015
Co-reporter:Yuan Ping;Cheng-De Liu;Gu-Ping Tang;Jian-Shu Li;Jun Li;Wan-Tai Yang
Advanced Functional Materials 2010 Volume 20( Issue 18) pp:3106-3116
Publication Date(Web):
DOI:10.1002/adfm.201000177
Abstract
It is of crucial importance to modify chitosan-based polysaccharides in the designing of biomedical materials. In this work, atom transfer radical polymerization (ATRP) was employed to functionalize chitosan in a well-controlled manner. A series of new degradable cationic polymers (termed as PDCS) composed of biocompatible chitosan backbones and poly((2-dimethyl amino)ethyl methacrylate) (P(DMAEMA)) side chains of different length were designed as highly efficient gene vectors via ATRP. These vectors, termed as PDCS, exhibited good ability to condense plasmid DNA (pDNA) into nanoparticles with positive charge at nitrogen/phosphorus (N/P) ratios of 4 or higher. All PDCS vectors could well protect the condensed DNA from enzymatic degradation by DNase I and they displayed high level of transfectivity in both COS7, HEK293 and HepG2 cell lines. Most importantly, in comparison with high-molecular-weight P(DMAEMA) and ‘gold-standard’ PEI (25 kDa), the PDCS vectors showed considerable buffering capacity in the pH range of 7.4 to 5, and were capable of mediating much more efficient gene transfection at low N/P ratios. At their own optimal N/P ratios for trasnsfection, the PDCS/pDNA complexes showed much lower cytotoxicity. All the PDCS vectors were readily to be degradable in the presence of lysozyme at physiological conditions in vitro. These well-defined PDCS polymers have great potentials as efficient gene vectors in future gene therapy.
Co-reporter:F. J. Xu, Y. Zhu, F. S. Liu, J. Nie, J. Ma and W. T. Yang
Bioconjugate Chemistry 2010 Volume 21(Issue 3) pp:456
Publication Date(Web):February 23, 2010
DOI:10.1021/bc900337p
Hydroxypropyl cellulose (HPC) possesses a lower critical solution temperature (LCST) above 40 °C, while the poly(N-isopropylacrylamide) (P(NIPAAm)) exhibits a LCST of about 32 °C. Herein, comb-shaped copolymer conjugates of HPC backbones and low-molecular-weight P(NIPAAm) side chains (HPC-g-P(NIPAAm) or HPN) were prepared via atom transfer radical polymerization (ATRP) from the bromoisobutyryl-functionalized HPC biopolymers. By changing the composition ratio of HPC and P(NIPAAm), the LCSTs of HPNs can be adjusted to be lower than the body temperature. The MTT assay from the HEK293 cell line indicated that HPNs possess reduced cytotoxicity. Some of the hydroxyl groups of HPNs were used as cross-linking sites for the preparation of stable HPN hydrogels. In comparison with the HPC hydrogels, the cross-linked HPN hydrogels possess interconnected pore structures and higher swelling ratios. The in vitro release kinetics of fluorescein isothiocyanate-labeled dextran and BSA (or dextran-FITC and BSA-FITC) as model drugs from the hydrogels showed that the HPN hydrogels are suitable for long-term sustained release of macromolecular drugs at body temperature.
Co-reporter:X. Lu, Y. Ping, F. J. Xu, Z. H. Li, Q. Q. Wang, J. H. Chen, W. T. Yang, and G. P. Tang
Bioconjugate Chemistry 2010 Volume 21(Issue 10) pp:1855
Publication Date(Web):September 20, 2010
DOI:10.1021/bc1002136
Earlier reports indicated that the conjugates (PEI600-CD, PC) of β-cyclodextrin and low-molecular-weight polyethylenimine (PEI, Mw 600) can be used as efficient gene carriers in glioma cancer therapy. Incorporating anticancer drugs onto PC conjugates may endow them with new and interesting properties for great applications. In this work, FU-PEI600-CD (FPC) conjugates comprising PC and 5-fluoro-2′-deoxyuridine (FdUrd) were prepared as new bifunctional anticancer prodrugs with improved therapeutic effects, as well as good gene transfer efficiency. In comparison with free FdUrd, FPC could inhibit proliferation and enhance cytotoxicity on glioma cells. The results of hematoxylin and eosin (HE) staining indicated that C6 cells treated with FPC shrunk more seriously. Unlike FdUrd, cell cycle analysis indicated that C6 cells were primarily arrested in the G1 phase in the presence of FPC. Cellular uptake of FPC in C6 cells was about 10 times higher than that of FdUrd. In addition, the in vitro and in vivo gene transfection indicated that FPC still exhibited good gene expression efficiency. With the ability to deliver drugs and transfer genes, such bifunctional FPC conjugates may have great potential applications in combination therapy of cancers.
Co-reporter:S. C. Tang, J. Y. Xie, Z. H. Huang, F. J. Xu and Wantai Yang
Langmuir 2010 Volume 26(Issue 12) pp:9905-9910
Publication Date(Web):May 20, 2010
DOI:10.1021/la100344f
We report a photolithographic process for micropatterning of two-component biomolecules on a transparent organic film via lateral functional polymer brushes of poly(sodium acrylate) (P(AA)) and poly(glycidyl methacrylate) (P(GMA)). The pattern of binary polymer brushes were prepared via consecutive UV-initiated grafting processes, under the assistance of the in situ formed poly (4,4′-bi[N-(4-vinylbenzyl) pyridinium]) (P(BVV)) photomask. The epoxy groups of the P(GMA) microdomains can be aminated for covalently coupling biotin, while the P(AA) microdomains were used for immobilizing immunoglobulin (IgG). The resulting biotin- and IgG-coupled microdomains interact specifically with their corresponding target proteins, avidin and anti-IgG, respectively.
Co-reporter:F. J. Xu, F. B. Su, S. B. Deng and W. T. Yang
Macromolecules 2010 Volume 43(Issue 5) pp:2630-2633
Publication Date(Web):February 4, 2010
DOI:10.1021/ma902080q
Novel stimuli-responsive polyelectrolyte, poly(N-benzyl-N′-(4-vinylbenzyl)-4,4′-bipyridium dichloride) or P(BpyClCl), brushes were prepared from the benzyl-chloride-immobilized SiO2 nanoparticles via surface-initiated atom transfer radical polymerization (ATRP). The dicationions (BV2+) of the P(BpyClCl) brushes can be reduced by UV irradiation to become radical monocations (BV+·), which can oxidize back to the original BV2+ state by exposure to air. The fast switching between dicationic and monocationic states of the P(BpyClCl) brushes on the SiO2 nanoparticles can be used as the physically controllable means for the reduction of metal ions (such as Au, Pt, and bimetallic Au/Pt ions) without the need for any added metal reduction agents.
Co-reporter:F. J. Xu, M. Y. Chai, W. B. Li, Y. Ping, G. P. Tang, W. T. Yang, J. Ma and F. S. Liu
Biomacromolecules 2010 Volume 11(Issue 6) pp:
Publication Date(Web):April 28, 2010
DOI:10.1021/bm100309y
Successful gene delivery vectors for clinical translation should have high transfection efficiency and minimal toxicity. In this work, well-defined poly(2-hydroxyl-3-(2-hydroxyethylamino)propyl methacrylate) (PGEA) vectors with flanking cationic secondary amine and nonionic hydroxyl units were prepared via the ring-opening reaction of the pendant epoxide groups of poly(glycidyl methacrylate) with the amine moieties of ethanolamine. It was found that PGEA carriers possess very low toxicity (<10% of the toxicity of branched polyethylenimine (PEI, 25 kDa), while exhibiting surprisingly excellent transfection efficiency (higher than or comparable to that of PEI (25 kDa)) in different cell lines. A series of transfection and cytotoxicity assays revealed that PGEAs are highly promising as a new class of safe and efficient gene delivery vectors for future clinical gene therapies.
Co-reporter:F.J. Xu, Z.H. Wang, W.T. Yang
Biomaterials 2010 31(12) pp: 3139-3147
Publication Date(Web):
DOI:10.1016/j.biomaterials.2010.01.032
Co-reporter:F.J. Xu, K.G. Neoh, E.T. Kang
Progress in Polymer Science 2009 Volume 34(Issue 8) pp:719-761
Publication Date(Web):August 2009
DOI:10.1016/j.progpolymsci.2009.04.005
Recent progress in controlled radical polymerizations, in particular atom transfer radical polymerization (ATRP), has provided a unique means for the design and synthesis of bioactive surfaces and functional biomaterials. This review summarizes such recent research activities. The synthesis strategies of bioactive surfaces and biomaterials via ATRP are described in detail. The highly robust and versatile ATRP technique is particularly suited for the preparation of functional bioactive surfaces, including antifouling, antibacterial, stimuli-responsive, biomolecule-coupled and micropatterned surfaces. In addition to bioactive surfaces, ATRP has also been widely used for the preparation of well-structured functional biomaterials, such as micellar delivery systems, hydrogels, cationic gene carriers and polymer–protein conjugates. The research activities in the last decade indicate that ATRP has become an essential tool for the design and synthesis of advanced, noble and novel biomaterials.
Co-reporter:F. J. Xu, Y. Ping, J. Ma, G. P. Tang, W. T. Yang, J. Li, E. T. Kang and K. G. Neoh
Bioconjugate Chemistry 2009 Volume 20(Issue 8) pp:1449
Publication Date(Web):July 31, 2009
DOI:10.1021/bc900044h
Cationic polymers have been of interest and importance as nonviral gene delivery carriers. Herein, well-defined comb-shaped cationic copolymers (HPDs) composed of long biocompatible hydroxypropyl cellulose (or HPC) backbones and short poly((2-dimethyl amino)ethyl methacrylate) (or P(DMAEMA)) side chains were prepared as gene vectors via atom transfer radical polymerization (ATRP) from the bromoisobutyryl-terminated HPC biopolymers. The P(DMAEMA) side chains of HPDs can be further partially quaternized to produce the quaternary ammonium HPDs (QHPDs). HPDs and QHPDs were assessed in vitro for nonviral gene delivery. HPDs exhibit much lower cytotoxicity and better gene transfection yield than high-molecular-weight P(DMAEMA) homopolymers. QHPDs exhibit a stronger ability to complex pDNA, due to increased surface cationic charges. Thus, the approach to well-defined comb-shaped cationic copolymers provides a versatile means for tailoring the functional structure of nonviral gene vectors to meet the requirements of strong DNA-condensing ability and high transfection capability.
Co-reporter:F. J. Xu, Z. X. Zhang, Y. Ping, J. Li, E. T. Kang and K. G. Neoh
Biomacromolecules 2009 Volume 10(Issue 2) pp:
Publication Date(Web):January 7, 2009
DOI:10.1021/bm8010165
Cationic polymers with low cytotoxicity and high transfection efficiency have attracted considerable attention as nonviral carriers for gene delivery. Herein, well-defined and star-shaped CDPD consisting of β-CD cores and P(DMAEMA) arms, and CDPDPE consisting of CDPD and P(PEGEEMA) end blocks (where CD = cyclodextrin, P(DMAEMA) = poly(2-(dimethylamino)ethyl methacrylate), P(PEGEEMA) = poly(poly(ethylene glycol)ethyl ether methacrylate)) for gene delivery were prepared via atom transfer radical polymerization (ATRP) from the bromoisobutyryl-terminated β-CD core. The CDPD and CDPDPE exhibit good ability to condense plasmid DNA (pDNA) into 100−200 nm size nanoparticles with positive zeta potentials of 25−40 mV at nitrogen/phosphate (N/P) ratios of 10 or higher. CDPD and CDPDPE exhibit much lower cytotoxicity and higher gene transfection efficiency than high molecular weight P(DMAEMA) homopolymers. A comparison of the transfection efficiencies between CDPD and P(DMAEMA) homopolymer indicates that the unique star-shaped architecture involving the CD core can enhance the gene transfection efficiency. In addition to reducing cytotoxicity, the introduction of a biocompatible P(PEGEEMA) end block to the P(DMAEMA) arms in CDPDPE can further enhance the gene transfection efficiency.
Co-reporter:F. J. Xu, L. Y. Liu, W. T. Yang, E. T. Kang and K. G. Neoh
Biomacromolecules 2009 Volume 10(Issue 6) pp:
Publication Date(Web):April 30, 2009
DOI:10.1021/bm900307c
Protein-resistant poly(poly(ethylene glycol)monomethacrylate)-graft-Si(100), or Si-g-P(PEGMA) hybrids, were prepared via surface-initiated atom transfer radical polymerization (ATRP) of the poly(ethylene glycol)monomethacrylate (PEGMA) macromonomer from the hydrogen-terminated Si(100) surface (Si−H surface). The resultant robust Si−C bonded P(PEGMA) brushes can be further functionalized by the immobilization of human immunoglobulin (IgG) protein via different strategies, namely, the direct use of the alkyl halide chain ends preserved throughout the ATRP process and the postmodification of the hydroxyl side chains with by 1,1′-carbonyldiimidazole (CDI) or succinic anhydride (SA). The CDI exhibited a higher efficiency in activating the hydroxyl groups for coupling proteins. The surface density of the immobilized protein above 2.5 μg/cm2 could be readily achieved. The distribution of active protein-docking sites on the Si−C bonded P(PEGMA) brushes can be also controlled by controlling the brush length. The resulting IgG-coupled Si-g-P(PEGMA) hybrid surface interacts only and specifically with the anti-IgG protein, while the dense P(PEGMA) brushes effectively prevent nonspecific protein binding and fouling. The simple concomitant incorporation of protein-resistant P(PEGMA) brushes and highly specific and active protein onto silicon surfaces via robust Si−C bonding should readily endow the silicon substrates with new and interesting properties for applications in silicon-based protein sensors or microarrays.
Co-reporter:Carl R. Moore
Science 1920 Vol 52(1338) pp:179-182
Publication Date(Web):20 Aug 1920
DOI:10.1126/science.52.1338.179
Co-reporter:R. H. True;P. G. Agnew
Science 1919 Vol 49(1273) pp:487-489
Publication Date(Web):23 May 1919
DOI:10.1126/science.49.1273.487
Co-reporter:Yajun Huang, Xiaokang Ding, Yu Qi, Bingran Yu, Fu-Jian Xu
Biomaterials (November 2016) Volume 106() pp:134-143
Publication Date(Web):November 2016
DOI:10.1016/j.biomaterials.2016.08.025
Co-reporter:Yajun Huang, Xiaokang Ding, Yu Qi, Bingran Yu, Fu-Jian Xu
Biomaterials (November 2016) Volume 106() pp:134-143
Publication Date(Web):November 2016
DOI:10.1016/j.biomaterials.2016.08.025
There is an increasing demand in developing of multifunctional materials with good antibacterial activity, biocompatibility and drug/gene delivery capability for next-generation biomedical applications. To achieve this purpose, in this work series of hydroxyl-rich hyperbranched polyaminoglycosides of gentamicin, tobramycin, and neomycin (HP and SS-HP with redox-responsive disulfide bonds) were readily synthesized via ring-opening reactions in a one-pot manner. Both HP and SS-HP exhibit high antibacterial activity toward Escherichia coli and Staphylococcus aureus. Meanwhile, the hemolysis assay of the above materials shows good biocompatibility. Moreover, SS-HPs show excellent gene transfection efficiency in vitro due to the breakdown of reduction-responsive disulfide bonds. For an in vivo anti-tumor assay, the SS-HP/p53 complexes exhibit potent inhibition capability to the growth of tumors. This study provides a promising approach for the design of next-generation multifunctional biomedical materials.
Co-reporter:Yue Sun, Hao Hu, Nana Zhao, Tian Xia, Bingran Yu, Chuanan Shen, Fu-Jian Xu.
Biomaterials (February 2017) Volume 117() pp:77-91
Publication Date(Web):February 2017
DOI:10.1016/j.biomaterials.2016.11.055
Co-reporter:F.J. Xu, K.G. Neoh, E.T. Kang
Progress in Polymer Science (August 2009) Volume 34(Issue 8) pp:719-761
Publication Date(Web):1 August 2009
DOI:10.1016/j.progpolymsci.2009.04.005
Recent progress in controlled radical polymerizations, in particular atom transfer radical polymerization (ATRP), has provided a unique means for the design and synthesis of bioactive surfaces and functional biomaterials. This review summarizes such recent research activities. The synthesis strategies of bioactive surfaces and biomaterials via ATRP are described in detail. The highly robust and versatile ATRP technique is particularly suited for the preparation of functional bioactive surfaces, including antifouling, antibacterial, stimuli-responsive, biomolecule-coupled and micropatterned surfaces. In addition to bioactive surfaces, ATRP has also been widely used for the preparation of well-structured functional biomaterials, such as micellar delivery systems, hydrogels, cationic gene carriers and polymer–protein conjugates. The research activities in the last decade indicate that ATRP has become an essential tool for the design and synthesis of advanced, noble and novel biomaterials.
Co-reporter:Y. Hu, N. N. Zhao, J. S. Li, W. T. Yang and F. J. Xu
Journal of Materials Chemistry A 2012 - vol. 22(Issue 39) pp:NaN21264-21264
Publication Date(Web):2012/08/28
DOI:10.1039/C2JM34919A
The inherent hydroxyl groups on the porous polycaprolactone (PPCL) films (prepared by using poly(ethylene glycol) as the pore-forming agent) could be reacted with 2-bromoisobutyrate bromide to produce a sufficient concentration of surface-coupled atom transfer radical polymerization (ATRP) initiators for the subsequent surface-initiated ATRP of thermo-responsive N-isopropylacrylamide (NIPAAm) at room temperature. A kinetics study revealed that the chain growth of the grafted NIPAAm polymer (P(NIPAAm)) was very fast and consistent with a ‘controlled’ process. The graft copolymerization not only occurred on the porous film surface, but also took place into the film bulk. The resultant P(NIPAAm)-grafted PPCL (PPCL-g-P(NIPAAm)) films assumed a uniform and interconnected porous structure and exhibited a temperature-sensitive property with a lower critical solution temperature (LCST) of about 32 °C, not unlike pure P(NIPAAm). The release of bovine serum albumin (BSA as a model protein) from the PPCL-g-P(NIPAAm) films was characterized by an initial burst, followed by a sustained release. These thermo-responsive PPCL-g-P(NIPAAm) porous films are potentially useful in biomedical fields.
Co-reporter:X. C. Yang, M. Y. Chai, Y. Zhu, W. T. Yang and F. J. Xu
Journal of Materials Chemistry A 2012 - vol. 22(Issue 16) pp:
Publication Date(Web):
DOI:10.1039/C2JM16166D
Co-reporter:H. Hu, X. B. Wang, S. L. Xu, W. T. Yang, F. J. Xu, J. Shen and C. Mao
Journal of Materials Chemistry A 2012 - vol. 22(Issue 30) pp:NaN15369-15369
Publication Date(Web):2012/06/07
DOI:10.1039/C2JM32720A
The ability to manipulate and control the surface properties of layered double hydroxide (LDH) nanoparticles is of crucial importance in the designing of LDH-based carriers of therapeutic agents. In this work, surface-initiated atom transfer radical polymerization (ATRP) of zwitterionic 3-dimethyl(methacryloyloxyethyl) ammonium propane sulfonate (DMAPS) is first employed to tailor the functionality of LDH surfaces in a well-controlled manner and produce a series of well-defined hemocompatible hybrids (termed as LDHPS). The blood compatibilities of the modified LDH nanoparticles were investigated using coagulation tests, complement activation, platelet activation, hemolysis assay, morphological changes of red blood cells, and cytotoxicity assay. The results confirmed that the P(DMAPS) grafting can substantially enhance the hemocompatibility of the LDH particles, and the LDHPS hybrids can be used as biomaterials without causing any hemolysis. With the versatility of surface-initiated ATRP and the excellent hemocompatibility of zwitterionic polymer chains, the LDH nanoparticles with desirable blood properties can be readily tailored to cater to various biomedical applications.
Co-reporter:Q. Cai, Y. Zhu, J. Q. He, Z. H. Wang, Fabing Su, F. J. Xu, X. P. Yang and W. T. Yang
Journal of Materials Chemistry A 2012 - vol. 22(Issue 18) pp:NaN9367-9367
Publication Date(Web):2012/03/15
DOI:10.1039/C2JM31109G
The ability to manipulate and control the surface properties of hydroxyapatite (HA) nanoparticles is of crucial importance for the design of HA-based carriers of therapeutic agents. In this work, surface-initiated atom transfer radical polymerization (ATRP) of (2-dimethyl amino)ethyl methacrylate (DMAEMA) is first employed to tailor the functionality of HA surfaces in a well-controlled manner and to produce a series of new cationic hybrids (termed as HA-PDM). The HA parts of HA-PDM were coated by different lengths of PDMAEMA chains. The HA-PDM exhibited a good ability to condense plasmid DNA (pDNA) with suitable particle size and a zeta potential for gene transfection. Most importantly, in comparison with PDMAEMA homopolymers, the HA-PDM displayed considerably enhanced buffering capacity, and exhibited much higher gene transfection efficiencies in different cell lines, including osteoblast MC3T3 and osteosarcoma MG63 cells. In addition, the HA-PDM/pDNA complexes also could largely enhance the differentiation of preosteoblast cells. Such well-defined HA-PDM nanohybrids possess great potential applications as new drug-delivery vectors in bone tissue engineering.
Co-reporter:Hui Jiang and Fu-Jian Xu
Chemical Society Reviews 2013 - vol. 42(Issue 8) pp:NaN3426-3426
Publication Date(Web):2013/01/24
DOI:10.1039/C2CS35453E
Functional polymer brushes have been utilized extensively for the immobilization of biomolecules, which is of crucial importance for the development of biosensors and biotechnology. Recent progress in polymerization methods, in particular surface-initiated atom transfer radical polymerization (ATRP), has provided a unique means for the design and synthesis of new biomolecule-functionalized polymer brushes. This current review summarizes such recent research activities. The different preparation strategies for biomolecule immobilization through polymer brush spacers are described in detail. The functional groups of the polymer brushes used for biomolecule immobilization include epoxide, carboxylic acid, hydroxyl, aldehyde, and amine groups. The recent research activities indicate that functional polymer brushes become versatile and powerful spacers for immobilization of various biomolecules to maximize their functionalities. This review also demonstrates that surface-initiated ATRP is used more frequently than other polymerization methods in the designs of new biomolecule-functionalized polymer brushes.
Co-reporter:Chen Xu, Bingran Yu, Hao Hu, Muhammad Naeem Nizam, Wei Yuan, Jie Ma and Fu-Jian Xu
Biomaterials Science (2013-Present) 2016 - vol. 4(Issue 8) pp:NaN1243-1243
Publication Date(Web):2016/07/04
DOI:10.1039/C6BM00360E
Lipids, as the greatest constituent in cell membranes, have been widely used for biomedical applications because of their excellent biological properties. The introduction of membrane lipid molecules into gene vectors would embody greater biocompatibility, cellular uptake and transfection efficiency. In this work, one flexible strategy for readily conjugating lipid molecules with polycations was proposed based on atom transfer radical polymerization to produce a series of cholesterol (CHO)- and phosphatidylinositol (PI)-terminated ethanolamine-functionalized poly(glycidyl methacrylate)s, namely CHO-PGEAs and PI-PGEAs, as effective gene carriers. CHO-PGEAs and PI-PGEAs truly demonstrated much better transfection performances compared to linear ethanolamine-functionalized poly(glycidyl methacrylate) (denoted as BUCT-PGEA) counterparts and traditional standard branched polythylenimine (PEI, 25 kDa). In addition, the good antitumor effects of CHO-PGEA and PI-PGEA were confirmed with suppressor tumor gene p53 systems in vitro and in vivo. The present work could provide a new strategy to develop effective cationic conjugation of lipid molecules for gene therapy.
![Oxirane, 2,2'-[dithiobis(2,1-ethanediyloxymethylene)]bis-](/data/chemimg/3777400/1251770-12-3.png)
![Oxirane, 2,2'-[dithiobis(2,1-ethanediyloxymethylene)]bis-](/data/chemimg/3777400/1251770-12-3_b.png)
