Co-reporter:Yajun Zhang;Zhengkui Zhang;Changren Liu;Weizhi Chen;Cheng Li;Wei Wu
Polymer Chemistry (2010-Present) 2017 vol. 8(Issue 10) pp:1672-1679
Publication Date(Web):2017/03/07
DOI:10.1039/C6PY01941B
Two types of water-soluble molecular brushes with a poly(3-phenylthiophene) (PPT) backbone tethering poly(ethylene glycol) (PEG) and zwitterionic poly(carboxybetaine) (PCB) side chains were synthesized and named PPTPEG and PPTPCB, respectively. Atomic force microscopy observations demonstrated their wormlike morphology with a length range of 5–33 nm. The two types of molecular brushes had similar emission spectra covering 500–800 nm with a maximal emission wavelength of about 590 nm in water. The fluorescence signals falling in 650–800 nm could penetrate deeper in tissues and improve the imaging properties of the brushes when they were used as optical probes. PPTPEG and PPTPCB brushes could be internalized by cells through caveolae-mediated endocytosis. The effects of PEG and PCB side chains of the brushes on their biological properties were compared, showing that the PCB side chain was favorable to the cellular uptake, tumor penetration and tumor targeting of the molecular brushes.
Co-reporter:Weizhi Chen;Shilu Ji;Xiaoping Qian;Yajun Zhang;Cheng Li;Wei Wu;Fei Wang
Polymer Chemistry (2010-Present) 2017 vol. 8(Issue 13) pp:2105-2114
Publication Date(Web):2017/03/28
DOI:10.1039/C7PY00330G
Packaging hydrophobic drugs into nanoparticles can improve their aqueous solubility, tumor-specific accumulation and therapeutic effect. In this study, we prepared phenylboronic acid-incorporated elastin-like polypeptide (ELP) nanoparticles by polymerizing N-3-acrylamidophenylboronic acid (APBA) in the presence of ELP which was expressed from a plasmid with the ELP gene in Escherichia coli. It was found that phenylboronic acid-incorporated elastin-like polypeptide nanoparticles (ELP-PAPBA NPs) had a spherical shape with the size of 100 nm and were highly stable in an aqueous medium with a wide range of pH. The cellular uptake experiment showed that the ELP-PAPBA NPs could be rapidly taken up by single cells and multicellular spheroids (MCs). However, the cellular uptake of ELP-PAPBA NPs decreased dramatically when tumor cells were pretreated with free APBA or free sialic acid, suggesting the interaction between boronic acid-incorporated nanoparticles and overexpressed sialic acid in cancer cells. When loaded with the drug doxorubicin (DOX), the ELP-PAPBA NPs showed a loading content of about 10% and an encapsulation efficiency of about 85%. Bio-distribution and in vivo anticancer efficiency experiments revealed that DOX-loaded ELP-PAPBA NPs had a better tumor accumulation and penetration, lower heart side effects and significant superior anticancer activity in H22 tumor-bearing mice compared to free DOX.
Co-reporter:Weizhi Chen;Liling Su;Peng Zhang;Cheng Li;Dan Zhang;Wei Wu
Polymer Chemistry (2010-Present) 2017 vol. 8(Issue 44) pp:6886-6894
Publication Date(Web):2017/11/14
DOI:10.1039/C7PY01389B
Herein, thermo and pH dual-responsive drug-linked pseudo-polypeptide micelles were prepared by a self-assembly strategy. Initially, a temperature-responsive comb-shaped poly(2-isopropyl-2-oxazoline)-b-linear poly(acrylic acid) block copolymer (CPiPrOx-b-PAA) was synthesized through a combination of living cationic ring-opening polymerization and living radical polymerization. Subsequently, conjugation of doxorubicin (DOX) with the linear PAA block through a pH-responsive acylhydrazone bond led to a block copolymer having an amphiphilic characteristic, and this block copolymer then self-assembled into CPiPrOx-b-PAA-DOX micelles. TEM and DLS measurements showed that the CPiPrOx-b-PAA-DOX micelles had a uniform spherical morphology with a solid size of about 50 nm and a hydrodynamic size of about 123 nm. Moreover, the micelle coating of comb-shaped poly(2-isopropyl-2-oxazoline) displayed a temperature-responsive behavior with a phase transition temperature of 45 °C. The CPiPrOx-b-PAA-DOX micelles showed a pH-responsive DOX release in vitro; this confirmed the acid-liable effect of the acylhydrazone bond that linked the linear PAA block with DOX. In in vitro cell test, a dose-dependent cytotoxicity and caveolae-mediated endocytosis of the CPiPrOx-b-PAA-DOX micelles were observed. Based on near-infrared fluorescence (NIRF) imaging, a significant tumor accumulation of the CPiPrOx-b-PAA-DOX micelles was observed when the dye-labeled CPiPrOx-b-PAA-DOX micelles were intravenously injected into H22 tumor-bearing mice.
Co-reporter:Xikuang Yao;Qiwen Zhu;Cheng Li;Kangjun Yuan;Rui Che;Peng Zhang;Chenchen Yang;Wei Lu;Wei Wu
Journal of Materials Chemistry B 2017 vol. 5(Issue 4) pp:834-848
Publication Date(Web):2017/01/25
DOI:10.1039/C6TB02863B
Conjugation of sugars to antitumor drugs can facilitate drug binding to tumor cells and the saccharide motifs of bleomycins (BLMs) play a crucial role in tumor-seeking. Here, we synthesized BLM monosaccharide, carbamoylmannose, and subsequently prepared carbamoylmannose decorated platinum-incorporating supramolecular nanoparticles formed through the host–guest complexation of poly(N-vinylpyrrolidone) and poly(aspartic acid). The targeting effects of carbamoylmannose decorated supramolecular nanoparticles in various cancer cells and tumor-bearing mice were investigated. It was found that the nanoparticles showed a specific in vitro and in vivo carbamoylmannose-mediated cellular uptake and drug delivery. The cellular uptake of the nanoparticles followed the receptor-mediated endocytosis mechanism in cancer cells but not in healthy cells. In a murine hepatic H22 tumor model, it was demonstrated that the carbamoylmannose moiety increased the plasma concentration, tumor targeting ability and tumor penetration of the nanoparticles, leading to high tumor accumulation and superior antitumor efficacy. This carbamoylmannose molecule may bring an opportunity to design and construct inexpensive but highly efficient drug and gene delivery systems in the future.
Co-reporter:Peng Zhang, Xiaoping Qian, Zhengkui Zhang, Cheng Li, Chen Xie, Wei Wu, and Xiqun Jiang
ACS Applied Materials & Interfaces 2017 Volume 9(Issue 7) pp:
Publication Date(Web):January 26, 2017
DOI:10.1021/acsami.6b14464
Supramolecular polymer micelles composed of seven-armed poly(2-methy-2-oxazoline) as the coating and linear poly(dl-lactide) as the core were prepared through synthesizing β-cyclodextrin-terminated poly(2-methy-2-oxazoline) and adamantine-terminated linear poly(dl-lactide), followed by host–guest interaction between β-cyclodextrin and adamantine groups in two polymers and self-assembly in aqueous solution. Dynamic light-scattering measurement showed that the micelles based on supramolecular amphiphilic polymers have the size of 119 nm and were highly stable in salt solution. When the micelles were used as the carrier of cabazitaxel, an antitumor agent for drug-resistant cancers, satisfactory drug loading content and encapsulation efficacy were obtained. In vitro cellular cytotoxicity assays found that cabazitaxel-loaded micelles presented obvious cytotoxicity against taxane-sensitive and -resistant cancer cells. Further in vivo antitumor activity evaluation showed that cabazitaxel-loaded micelles have significantly superior efficacy in inhibiting tumor growth and prolonging survival in tumor-bearing mice compared to that of free paclitaxel and free cabazitaxel.Keywords: antitumor activity; drug delivery; poly(2-methy-2-oxazoline); pseudo-block copolymers; supramolecular polymer micelles;
Co-reporter:Jialiang Zhang, Zhengkui Zhang, Bo Yu, Chen Wang, Wei Wu, and Xiqun Jiang
ACS Applied Materials & Interfaces 2016 Volume 8(Issue 9) pp:5794
Publication Date(Web):February 19, 2016
DOI:10.1021/acsami.5b10876
To understand the size effect of polymeric micelles on their biological properties, such as cellular uptake, biodistribution, tumor accumulation, and so on, we prepared a series of doxorubicin (DOX)-loaded protoporphyrin (PP)-poly(ε-caprolactone) (PCL)-poly(ethylene glycol) (PEG) micelles with different diameters (40, 70, 100, and 130 nm). The incorporation of the protoporphyrin moiety enhanced the stability of the micelles and provided luminescent capability that is useful in the investigation of the cellular uptake of the micelles by fluorescence imaging. The biodistributions of the micelles in mice bearing tumors were evaluated by near-infrared fluorescence imaging and DOX concentration measurements in different tissues. The in vitro and in vivo investigations demonstrated the pronounced dependence of the cellular uptake, biodistribution, and antitumor effectiveness of the micelles on their size.Keywords: biodistribution; cellular uptake; polymeric micelles; protoporphyrin; size dependence
Co-reporter:Yajun Zhang, Weizhi Chen, Chenchen Yang, Quli Fan, Wei Wu, Xiqun Jiang
Journal of Controlled Release 2016 Volume 237() pp:115-124
Publication Date(Web):10 September 2016
DOI:10.1016/j.jconrel.2016.07.011
We report a strategy to significantly improve tumor penetration of nanomedicines by using size-minimized and zwitterionic nanocarriers. We synthesized a series of 21-arm star block copolymers with the hydrodynamic diameter of 10–40 nm and conjugated doxorubicin to the copolymers through pH-sensitive acylhydrazone linkages. The zwitterionic poly(carboxybetaine) (PCB), nonionic polyethylene glycol (PEG) and phenylboronic acid-incorporated PCB were selected as the peripherial hydrophilic blocks of the copolymers, respectively. We demonstrated that the size-minimized multiarm copolymer with PCB surface showed stronger tumor permeability when compared to the copolymers with PEG surface or larger size. The drug-conjugated multiarm copolymer that has the longest blood circulation time did not achieve the highest tumor accumulation. The incorporation of phenylboronic acid group into the peripherial block of the drug-conjugated multiarm copolymer significantly enhanced their cytotoxicity, cellular uptake, tumor accumulation, tumor permeability and antitumor activity.The effects of size, hydrophilic block and targeting moiety on tumor accumulation and tumor penetration of the 21 arm star block copolymers were investigated in cellular and tissue levels.
Co-reporter:Jing Wang, Shanmei Yuan, Yajun Zhang, Wei Wu, Yong Hu and Xiqun Jiang
Biomaterials Science 2016 vol. 4(Issue 9) pp:1351-1360
Publication Date(Web):18 Jul 2016
DOI:10.1039/C6BM00201C
Zwitterionic poly(carboxybetaine) (PCB), poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) and non-ionic poly(ethylene glycol) (PEG), which have similar degrees of polymerization, were grafted to branched polyethyleneimine (PEI) to generate PCB-grafted PEI (PEI-PCB), PMPC-grafted PEI (PEI-PMPC) and PEG-grafted PEI (PEI-PEG) copolymers, respectively. These grafted PEI copolymers with almost the same grafting number were coated on the surface of 110 nm bovine serum albumin-poly(N-3-acrylamidophenylboronic acid) (BSA-PAPBA) nanoparticles to make a comparison of the surface decoration effect on the biodistribution of nanoparticles. Compared to the nanoparticles without surface decoration, surface decoration with the copolymers significantly prolonged the circulation time of BSA-PAPBA nanoparticles, leading to remarkable enhancement of tumor uptake of the nanoparticles. The drug accumulation at the tumor site reached more than 10% injected dose per gram of tumor. Among them, the PEI-PMPC-decorated nanoparticles exhibited the best performance in tumor accumulation and anticancer ability. Thus, these surface-decorated nanoparticles may serve as a strong candidate for high tumor accumulation of drug delivery systems.
Co-reporter:Chen Xie, Peng Zhang, Zhengkui Zhang, Chenchen Yang, Jialiang Zhang, Wei Wu and Xiqun Jiang
Nanoscale 2015 vol. 7(Issue 29) pp:12572-12580
Publication Date(Web):15 Jun 2015
DOI:10.1039/C5NR02861B
Supramolecular constructed pseudo block copolymer micelles based on β-cyclodextrin terminated 4 and 7 armed star poly(N-vinylpyrrolidone) and adamantane terminated linear poly(ε-caprolactone) were prepared. The size, morphology, stability and protein adsorption were experimentally examined. The micelles with 7 armed PVP chains as the micellar exterior showed the lowest amount of protein adsorption and the best stability in media. When cabazitaxel, a new taxane, was loaded into the micelles, 14.4% drug loading content and 85% encapsulation efficacy were achieved. In vitro cytotoxicity studies demonstrated that the cabazitaxel-loaded micelles show significant cytotoxicity against drug-resistant A2780/T cell lines. Biodistribution studies showed that the micelles can almost double the content of cargo in tumor sites compared with the free cargo. In vivo antitumor activity examinations indicated that cabazitaxel-loaded micelles show superior antitumor activity over free paclitaxel and free cabazitaxel.
Co-reporter:Ying Lin, Sanxi Wang, Yajun Zhang, Jiangang Gao, Liu Hong, Xin Wang, Wei Wu and Xiqun Jiang
Journal of Materials Chemistry A 2015 vol. 3(Issue 28) pp:5702-5710
Publication Date(Web):28 May 2015
DOI:10.1039/C5TB00593K
Superparamagnetic iron oxide nanoparticles encapsulated in hydrophilic chitosan nanospheres were prepared by nonsolvent-aided counterion complexation completely in an aqueous solution. The T2 relaxation of these hybrid nanospheres in vitro and in vivo was investigated. It was found that the molar transverse relaxivity rate r2 of hybrid nanospheres highly depends upon the payload of iron oxide nanoparticles within hybrid nanospheres. Compared to free iron oxide nanoparticles, the molar transverse relaxivity rate, r2 of hybrid nanospheres shows an approximately 8-fold increase and reaches the maximum of 533 Fe mM−1 s−1. Such a high r2 value is probably associated with the clustering effect of iron oxide nanoparticles, which are confined in the chitosan nanospheres. The in vivo magnetic resonance imaging (MRI) demonstrates that the hybrid nanospheres shorten transverse relaxation time, T2 and significantly decrease the signal intensity of the tumor area, giving rise to high contrast tumor MR imaging at a relatively low dose.
Co-reporter:Chenchen Yang, Xin Wang, Xikuang Yao, Yajun Zhang, Wei Wu, Xiqun Jiang
Journal of Controlled Release 2015 Volume 205() pp:206-217
Publication Date(Web):10 May 2015
DOI:10.1016/j.jconrel.2015.02.008
A methacrylation strategy was employed to functionalize hyaluronic acid and prepare hyaluronic acid (HA) nanogels. Dynamic light scattering, zeta potential analyzer and electron microscopy were utilized to characterize the nanogels and their enzyme-degradability in vitro. It was found that these nanogels had a spherical morphology with the diameter of about 70 nm, and negative surface potential. When doxorubicin (DOX) was loaded into the nanogels, the diameter decreased to approximately 50 nm with a drug loading content of 16% and encapsulation efficiency of 62%. Cellular uptake examinations showed that HA nanogels could be preferentially internalized by two-dimensional (2D) cells and three-dimensional (3D) multicellular spheroids (MCs) which both overexpress CD44 receptor. Near-infrared fluorescence imaging, biodistribution and penetration examinations in tumor tissue indicated that the HA nanogels could efficiently accumulate and penetrate the tumor matrix. In vivo antitumor evaluation found that DOX-loaded HA nanogels exhibited a significantly superior antitumor effect.Doxorubicin-loaded hyaluronic acid nanogels were synthesized by a methacrylated strategy. In vitro cellular uptake shows that these nanogels were preferentially internalized by the CD44 or CD168-overexpressed cancer cells. In vivo antitumor examination indicates that these nanogels suppress tumor growth distinctly.
Co-reporter:Chen Xie, Chenchen Yang, Peng Zhang, Jialiang Zhang, Wei Wu and Xiqun Jiang
Polymer Chemistry 2015 vol. 6(Issue 10) pp:1703-1713
Publication Date(Web):15 Jan 2015
DOI:10.1039/C4PY01722F
A new kind of drug-crosslinked polymer nanoparticle was prepared. The nanoparticles were composed of a phenylboronic acid modified hydroxycamptothecin crosslinker (HCPT-diHMPBA) and a 1,2-diol-rich poly(ethylene oxide)-b-poly(glycerol monomethacrylate) diblock copolymer (PEG-PGMA), and crosslinked by a phenylboronic ester bond. Dynamic light scattering measurement and electron microscopy observation revealed that the nanoparticles had a spherical morphology with a hydrodynamic diameter of 146 nm. The phenylboronic acid modified hydroxycamptothecin crosslinker could be released from the nanoparticles in a sustained manner and converted into pharmaceutically active hydroxycamptothecin (HCPT) in an enzyme-containing medium, as shown in the in vitro cytotoxicity test. Cellular uptake examination by confocal laser scanning microscopy showed that the nanoparticles were well internalized by cancer cells and active HCPT was found inside the cells.
Co-reporter:Xianchuang Zheng;Huang Tang;Chen Xie;Jialiang Zhang; Wei Wu ; Xiqun Jiang
Angewandte Chemie International Edition 2015 Volume 54( Issue 28) pp:8094-8099
Publication Date(Web):
DOI:10.1002/anie.201503067
Abstract
We have developed a nanosensor for tracking cancer metastasis by noninvasive real-time whole-body optical imaging. The nanosensor is prepared by the formation of co-micelles from a poly(N-vinylpyrrolidone)-conjugated iridium(III) complex (Ir-PVP) and poly(ε-caprolactone)-b-poly(N-vinylpyrrolidone) (PCL-PVP). The near-infrared phosphorescence emission of the nanosensor could be selectively activated in the hypoxic microenvironment induced by cancer cells. The detection ability of the nanosensor was examined in cells and different animal models. After intravenous injection, the nanosensor can be effectively delivered to the lung and lymph node, and cancer cell metastasis through bloodstream or lymphatics can be quickly detected with high signal-to-background ratio by whole-body imaging and organ imaging. Moreover, the nanosensor exhibits good biocompatibility both in vitro and in vivo. The nanosensor is believed to be a powerful tool for the diagnosis of cancer metastasis.
Co-reporter:Xikuang Yao, Chen Xie, Weizhi Chen, Chenchen Yang, Wei Wu, and Xiqun Jiang
Biomacromolecules 2015 Volume 16(Issue 7) pp:
Publication Date(Web):May 29, 2015
DOI:10.1021/acs.biomac.5b00479
Cisplatin-incorporating pseudoblock copolymer nanoparticles with high drug loading efficiency (ca. 50%) were prepared built on host–guest inclusion complexation between β-cyclodextrin end-capped poly(N-vinylpyrrolidone) block and admantyl end-capped poly(aspartic acid) block, followed by the coordination between cisplatin and carboxyl groups in poly(aspartic acid). The host–guest interaction between the two polymer blocks was examined by two-dimensional nuclear overhauser effect spectroscopy. The size and morphology of nanoparticles formed were characterized by dynamic light scattering, zeta potential, transmission electron microscopy, and atomic force microscopy. The size control of nanoparticles was carried out by varying the ratio of poly(N-vinylpyrrolidone) to poly(aspartic acid). The nanoparticles were stable in the aqueous medium with different pH values but disintegrated in the medium containing Cl– ions. The in vitro and in vivo antitumor effects of cisplatin-loaded nanoparticles were evaluated. The biodistribution of the nanoparticles in vivo was studied by noninvasive near-infrared fluorescence imaging and ion-coupled plasma mass spectrometry. It was found that cisplatin-loaded nanoparticles could effectively accumulate in the tumor site and exhibited significant superior in vivo antitumor activity to the commercially available free cisplatin by combining the tumor volume, body weight, and survival rate measurements.
Co-reporter:Xianchuang Zheng;Huang Tang;Chen Xie;Jialiang Zhang; Wei Wu ; Xiqun Jiang
Angewandte Chemie International Edition 2015 Volume 54( Issue 28) pp:
Publication Date(Web):
DOI:10.1002/anie.201582861
Co-reporter:Wei Wu, Wei Yao, Xin Wang, Chen Xie, Jialiang Zhang, Xiqun Jiang
Biomaterials 2015 39() pp: 260-268
Publication Date(Web):
DOI:10.1016/j.biomaterials.2014.11.005
Co-reporter:Xianchuang Zheng;Huang Tang;Chen Xie;Jialiang Zhang; Wei Wu ; Xiqun Jiang
Angewandte Chemie 2015 Volume 127( Issue 28) pp:8212-8217
Publication Date(Web):
DOI:10.1002/ange.201503067
Abstract
We have developed a nanosensor for tracking cancer metastasis by noninvasive real-time whole-body optical imaging. The nanosensor is prepared by the formation of co-micelles from a poly(N-vinylpyrrolidone)-conjugated iridium(III) complex (Ir-PVP) and poly(ε-caprolactone)-b-poly(N-vinylpyrrolidone) (PCL-PVP). The near-infrared phosphorescence emission of the nanosensor could be selectively activated in the hypoxic microenvironment induced by cancer cells. The detection ability of the nanosensor was examined in cells and different animal models. After intravenous injection, the nanosensor can be effectively delivered to the lung and lymph node, and cancer cell metastasis through bloodstream or lymphatics can be quickly detected with high signal-to-background ratio by whole-body imaging and organ imaging. Moreover, the nanosensor exhibits good biocompatibility both in vitro and in vivo. The nanosensor is believed to be a powerful tool for the diagnosis of cancer metastasis.
Co-reporter:Xianchuang Zheng;Huang Tang;Chen Xie;Jialiang Zhang; Wei Wu ; Xiqun Jiang
Angewandte Chemie 2015 Volume 127( Issue 28) pp:
Publication Date(Web):
DOI:10.1002/ange.201582861
Co-reporter:Wei Wu ; Wouter Driessen
Journal of the American Chemical Society 2014 Volume 136(Issue 8) pp:3145-3155
Publication Date(Web):February 7, 2014
DOI:10.1021/ja411457r
Dendrimers have several featured advantages over other nanomaterials as drug carriers, such as well-defined structure, specific low-nanometer size, and abundant peripheral derivable groups, etc. However, these advantages have not been fully exploited yet to optimize their biological performance, especially tumor penetration, which is a shortcoming of current nanomaterials. Here we show the syntheses of a new class of oligo(ethylene glycol) (OEG)-based thermosensitive dendrimers up to the fourth generation. Each dendrimer shows monodisperse structure. OEG/poly(ethylene glycol) (PEG) moieties with different precise lengths were introduced to the periphery of the fourth-generation dendrimer followed by an antitumor agent, gemcitabine (GEM). The biodistributions of the GEM-conjugated dendrimers were investigated by micro positron emission tomography and multispectral optoacoustic tomography imaging techniques and compared with that of GEM-conjugated poly(amidoamine) (PAMAM). The GEM-conjugated dendrimer with the longest peripheral PEG segments exhibited the most desirable tumor accumulation and penetration and thus had significantly higher antitumor activity than the GEM-conjugated PAMAM.
Co-reporter:Ying Chen, Xianchuang Zheng, Xin Wang, Chongzhi Wang, Yin Ding, and Xiqun Jiang
ACS Macro Letters 2014 Volume 3(Issue 1) pp:74
Publication Date(Web):December 30, 2013
DOI:10.1021/mz4005748
A facile synthesis of near-infrared (NIR) luminescent gold cluster–poly(acrylic acid) (PAA) hybrid nanogels was developed by in situ reduction of gold salt in the core-hollow and shell-porous PAA nanogels. These Au-PAA nanogels exhibited excellent near-infrared photoluminescence properties and showed targeting potential in the optical imaging of the living body.
Co-reporter:Hanqing Qian, Xin Wang, Kangjun Yuan, Chen Xie, Wei Wu, Xiqun Jiang and Lijiang Hu
Biomaterials Science 2014 vol. 2(Issue 2) pp:220-232
Publication Date(Web):07 Oct 2013
DOI:10.1039/C3BM60176E
A methacrylation strategy was used to functionalize carboxymethyl cellulose and prepare redox-sensitive cellulose nanogels which contained disulfide bonds. Dynamic light scattering, zeta potential and electron microscopy were utilized to characterize these nanogels. It was found that these nanogels had a spherical morphology with a diameter of about 192 nm, and negative surface potential. These redox-sensitive nanogels were stable against high salt concentration but de-integrated in the reducing environment containing glutathione. When doxorubicin (DOX) was loaded into the nanogels, a high drug loading content (36%) and a high encapsulation efficiency (83%) were achieved. Confocal laser scanning microscopy and co-localization images showed that DOX-loaded nanogels were internalized by the cancer cells through endocytosis and the DOX could be delivered into the nucleus. Near-infrared fluorescence imaging biodistribution examination indicated that the nanogels could passively target to the tumor area by the EPR effect and had a significantly prolonged circulation time. In vivo antitumor evaluation found that DOX-loaded nanogels exhibited a significantly superior antitumor effect than the free DOX by combining the tumor volume measurement and the examination of cell apoptosis and proliferation in tumor tissues.
Co-reporter:Xu Zhen;Xin Wang;Chenchen Yang;Qin Liu;Wei Wu;Baorui Liu
Macromolecular Bioscience 2014 Volume 14( Issue 8) pp:1149-1159
Publication Date(Web):
DOI:10.1002/mabi.201400018
Abstract
Whey-poly(acrylic acid) (whey-PAA) nanoparticles are prepared by polymerizing acrylic acid (AA) monomer in the presence of whey protein in a complete aqueous medium. The properties, drug loading, and release as well as in vitro cytotoxicity of whey-PAA nanoparticles are examined. The cellular uptakes and penetration of nanoparticle in the SH-SY5Y monolayer cells and multicellular tumor spheroids are observed. The in vivo distribution of the nanoparticles in tumor-bearing mice is evaluated. Confocal laser scanning microscopy and co-localization images show that the nanoparticles are well internalized by the cells through the endocytosis mechanism. Drug-loaded whey-PAA nanoparticles can penetrate multicellular tumor spheroids more deeply. In vivo near-infrared fluorescence imaging examination and in vivo DOX distribution show that the drug-loaded whey-PAA nanoparticles can well accumulated in the tumor site. Thus, these whey-rich nanoparticles seem to be very promising drug carriers for drug delivery.
Co-reporter:Jingjing Wang;Zhaoheng Zhang;Wei Wu
Chinese Journal of Chemistry 2014 Volume 32( Issue 1) pp:78-84
Publication Date(Web):
DOI:10.1002/cjoc.201300737
Abstract
A water soluble β-cyclodextrin (β-CD) functionalized [60]fullerene (C60-CD) was synthesized. The C60-CD-induced generation of reactive oxygen species (ROS), and DNA-cleavage ability and cytotoxicity of C60-CD were studied upon visible light irradiation, demonstrating that the compound is very promising in the applications of photodynamic therapy. The histological analyses demonstrate that C60-CD has no acute or subacute toxicity to living body.
Co-reporter:Jing Wang, Wei Wu, Yajun Zhang, Xin Wang, Hanqing Qian, Baorui Liu, Xiqun Jiang
Biomaterials 2014 35(2) pp: 866-878
Publication Date(Web):
DOI:10.1016/j.biomaterials.2013.10.028
Co-reporter:Xin Wang, Chenchen Yang, Yajun Zhang, Xu Zhen, Wei Wu, Xiqun Jiang
Biomaterials 2014 35(24) pp: 6439-6453
Publication Date(Web):
DOI:10.1016/j.biomaterials.2014.04.016
Co-reporter:Jing Wang, Kejian Yao, Chongzhi Wang, Chuanbing Tang and Xiqun Jiang
Journal of Materials Chemistry A 2013 vol. 1(Issue 17) pp:2324-2332
Publication Date(Web):05 Mar 2013
DOI:10.1039/C3TB20100G
Well-defined amphiphilic poly(ethylene glycol) and poly(dehydroabietic ethyl methacrylate) block copolymers (PEG-b-PDAEMA) were prepared by atom transfer radical polymerization. The methacrylate block contains a characteristic hydrophobic, biocompatible and economical dehydroabietic moiety. PEG-b-PDAEMA block copolymer micellar nanoparticles loaded with piperlongumine (PLGM) were successfully prepared by a nanoprecipitation method. In vitro and in vivo behaviors of these nanoparticles were thoroughly examined by a set of characterization techniques. Confocal laser scanning microscopy study revealed that these nanoparticles could be well taken up by cancer cells. In vivo near-infrared fluorescence imaging showed that the PLGM-loaded nanoparticles effectively targeted the tumor site by the enhanced permeability and retention (EPR) effect in H22 tumor-bearing mice. The in vivo antitumor examination found that PLGM-loaded nanoparticles exhibited superior efficacy in impeding the tumor growth compared to the commercially available Taxol® and free PLGM formulation. The changes in body weights and blood biochemical profiles were also compared to investigate the safety of PLGM and PEG-b-PDAEMA nanoparticle drug delivery system.
Co-reporter:Jing Wang, Zhaoheng Zhang, Xin Wang, Wei Wu, Xiqun Jiang
Journal of Controlled Release 2013 Volume 168(Issue 1) pp:1-9
Publication Date(Web):28 May 2013
DOI:10.1016/j.jconrel.2013.02.019
40 nm-sized boronic acid-rich protein nanoparticles composed of bovine serum albumin and poly(N-3-acrylamidophenylboronic acid) were prepared by polymerizing N-3-acrylamidophenylboronic acid in the presence of albumin. The content of boronic acid-containing poly(N-3-acrylamidophenylboronic acid) in the nanoparticles can be tuned from 80% to 32% at constant nanoparticle size. When used to deliver doxorubicin in vivo, such sized nanoparticles show dominantly liver-targeting, and significant washout-resistant ability compared to those boronic acid-absent nanoparticles due to the interaction between sialic acid residues in the liver and boronic acid groups in the nanoparticles. The sialic acid overexpression on hepatic H22 tumor cells is demonstrated to be much higher than that on hepatocytes, resulting in the preferential accumulation of boronic acid-rich nanoparticles in liver cancer cells. In vivo antitumor examination in orthotopic liver cancer model shows that these doxorubicin-loaded nanoparticles not only have significantly superior ability in impeding tumor growth, but also induce distinct tumor regression with no hepatic and cardiac toxicities.Doxorubicin was encapsulated in boronic acid-rich protein nanoparticles. In vivo antitumor examination in orthotopic liver cancer shows that these nanoparticles make tumor regression distinctly.
Co-reporter:Jingjing Wang, Jialiang Zhang, Shuling Yu, Wei Wu, and Xiqun Jiang
ACS Macro Letters 2013 Volume 2(Issue 1) pp:82
Publication Date(Web):December 31, 2012
DOI:10.1021/mz300538u
Giant multiarm polymers with and without β-cyclodextrin (β-CD) end groups were synthesized. Further, the former was assembled into nanoparticles via a β-CD/adamantane inclusion complex. The incorporation of an esterase-sensitive linker in the inclusion complex enables the nanoparticles to decompose to the multiarm polymer again through the hydrolysis of ester linkage, making the nanoparticles have the characteristics of multistage nanovectors.
Co-reporter:Bengang Li, Qing Wang, Xin Wang, Chongzhi Wang, Xiqun Jiang
Carbohydrate Polymers 2013 Volume 93(Issue 2) pp:430-437
Publication Date(Web):2 April 2013
DOI:10.1016/j.carbpol.2012.12.051
Amphiphilic dextran-b-poly(ɛ-caprolactone) diblock copolymers were synthesized with the purpose of preparing nanocarriers for doxorubicin (DOX), an anticancer drug. The Dex-b-PCL diblock copolymers were synthesized by end-to-end coupling of amino-terminated dextran and aldehyde-terminated poly(ɛ-caprolactone) and characterized by 1H NMR spectra and gel permeation chromatography. The DOX-loaded Dex-b-PCL nanoparticles were prepared by a modified nanoprecipitation method and characterized by transmission electron microscopy and dynamic light scattering. In vitro release of DOX from DOX-Dex-b-PCL nanoparticles showed a sustained release manner with certain amount of burst release in the first 9 h. In vitro cytotoxicity test of DOX-Dex-b-PCL nanoparticles against SH-SY5Y cells showed that DOX is still pharmacologically active after drug loading. The fluorescence imaging results showed that DOX-Dex-b-PCL nanoparticles could be easily uptaken by SH-SY5Y cells. These results indicate that DOX-Dex-b-PCL nanoparticles may be a promising nanocarrier for DOX.Highlights► Dextran-b-PCL diblock copolymers were synthesized by the end-to-end coupling between dextran and poly(ɛ-caprolactone). ► Drug-loaded dextran-b-PCL nanoparticles were prepared by a modified nanoprecipitation method. ► In vitro release of drug from dextran-b-PCL nanoparticles showed a sustained release manner. ► The fluorescence imaging showed that Dex-b-PCL nanoparticles could be easily uptaken by cancer cells.
Co-reporter:Rui Chen, Xianchuang Zheng, Hangqing Qian, Xin Wang, Jing Wang and Xiqun Jiang
Biomaterials Science 2013 vol. 1(Issue 3) pp:285-293
Publication Date(Web):06 Nov 2012
DOI:10.1039/C2BM00138A
Motivated by the enhanced cytotoxicity of some chemotherapeutic agents at temperature rise, multifunctional chitosan nanospheres which co-carried gold nanorods and cisplatin were prepared. These hybrid nanospheres were characterized by dynamic light scattering, zeta potential, UV-Vis absorption spectra and transmission electron microscopy. It was demonstrated that these 120 nm-sized hybrid nanospheres could be selectively accumulated at the tumor site with about 11% injection dose per g of tumor, and produced local hyperthermia to an average temperature of 49 °C in tumor tissue after near-IR irradiation for 10 min. Due to the enhanced cytotoxicity of cisplatin at elevated temperatures, cisplatin-loaded hybrid nanospheres showed about one-second lower IC50 values than hybrid nanospheres alone in vitro and almost complete tumor growth inhibition in vivo. Compared with chemotherapy or photothermal treatment alone, the combined photothermal therapy and chemotherapy had a significantly synergistic effect and improved the therapeutic efficacy, which was supported by immunofluorescence staining and in vivo apoptosis imaging.
Co-reporter:Xin Wang, Xu Zhen, Jing Wang, Jialiang Zhang, Wei Wu, Xiqun Jiang
Biomaterials 2013 34(19) pp: 4667-4679
Publication Date(Web):
DOI:10.1016/j.biomaterials.2013.03.008
Co-reporter:Lu-zhong Zhang;Ya-jun Zhang;Wei Wu 武伟
Chinese Journal of Polymer Science 2013 Volume 31( Issue 5) pp:778-786
Publication Date(Web):2013 May
DOI:10.1007/s10118-013-1267-y
The in vivo behaviors of doxorubicin (DOX)-loaded dextran-poly(3-acrylamidophenylboronic acid) (Dextran-PAPBA) nanoparticles (NPs) were studied. The DOX-loaded NPs had a narrowly distributed diameter of ca. 74 nm and mainly accumulated in liver of tumor-bearing mice after intravenous injection as demonstrated by in vivo real-time near infrared fluorescent imaging. The DOX contents in various tissues were quantified and consisted well with the results of fluorescent imaging. The biodistribution pattern of DOX-loaded NPs encourages us to investigate their liver tumor treatment by using an orthotopically implanted liver tumor model, revealing that the DOX-loaded NPs formulation had better antitumor effect than free DOX.
Co-reporter:Rui Chen, Xin Wang, Xikuan Yao, Xianchuang Zheng, Jing Wang, Xiqun Jiang
Biomaterials 2013 34(33) pp: 8314-8322
Publication Date(Web):
DOI:10.1016/j.biomaterials.2013.07.034
Co-reporter:Shuling Yu;Yajun Zhang;Xin Wang;Xu Zhen;Zhaoheng Zhang;Dr. Wei Wu; Xiqun Jiang
Angewandte Chemie International Edition 2013 Volume 52( Issue 28) pp:7272-7277
Publication Date(Web):
DOI:10.1002/anie.201301397
Co-reporter:Xu Zhen, Xin Wang, Chen Xie, Wei Wu, Xiqun Jiang
Biomaterials 2013 34(4) pp: 1372-1382
Publication Date(Web):
DOI:10.1016/j.biomaterials.2012.10.061
Co-reporter:Ying Lin, Wei Yao, Yuan Cheng, Hanqing Qian, Xin Wang, Yin Ding, Wei Wu and Xiqun Jiang
Journal of Materials Chemistry A 2012 vol. 22(Issue 12) pp:5684-5693
Publication Date(Web):10 Feb 2012
DOI:10.1039/C2JM15133B
ZnFe2O4 nanoparticles were tightly packed and encapsulated in chitosan nanospheres by a nonsolvent-aided counterion complexation method. The obtained hybrid nanospheres exhibited not only the superparamagnetic properties provided by pure ZnFe2O4 nanoparticles but also a much higher r2 relaxivity value than separate ZnFe2O4 nanoparticles, representing an approximately 3 to 16 fold increase. This was attributed to the high ZnFe2O4 payload and ZnFe2O4 nanoparticle clustering effect in the core of the nanospheres. The MR images generated in vivo demonstrated that the hybrid nanospheres showed an excellent contrast in T2 weighted MRI and a high MRI sensitivity in the tumor sites for both passive and active targeting samples. In addition, the biodistribution analysis revealed that the obtained hybrid nanospheres could accumulate at tumor sites via passive and active targeting strategies.
Co-reporter:Wei Yao, Hanqing Qian, Jialiang Zhang, Wei Wu and Xiqun Jiang
Chemical Communications 2012 vol. 48(Issue 56) pp:7079-7081
Publication Date(Web):24 May 2012
DOI:10.1039/C2CC32387G
A polymeric multivesicular system was created by hydrating a film. This system underwent multifusion events and eventually evolved into giant multilamellar vesicles with extremely thick walls. The semi-permeable wall and large size make these vesicles suitable for encapsulating living cells.
Co-reporter:Dan Ding, Jing Wang, Zhenshu Zhu, Rutian Li, Wei Wu, Baorui Liu, and Xiqun Jiang
ACS Applied Materials & Interfaces 2012 Volume 4(Issue 3) pp:1838
Publication Date(Web):February 24, 2012
DOI:10.1021/am300138z
In this report, the cisplatin (CDDP)-loaded gelatin/poly(acrylic acid) (GEL-PAA) nanoparticles with a spherical shape and drug loading content of 24.6% were prepared. In vivo near-infrared fluorescence (NIRF) imaging and ex vivo gamma scintillation counting analyses reveal that CDDP-loaded GEL-PAA nanoparticles have prominent passive tumor-targeting ability and the nontarget nanoparticles can be readily excreted from the body. Further, it is demonstrated that the CDDP-loaded nanoparticles have the ability to penetrate the tumor after their extravasation through the leaky vessels and distribute in a distance of about 20 μm from the vessels at 24 h postinjection. The in vivo antitumor responses reveal that the nanoparticle formulation exhibits significantly superior in vivo antitumor effect than free CDDP by the comparison of tumor volume and the examinations of cell apoptosis and proliferation in tumor tissues through proliferating cell nuclear antigen (PCNA) and terminal deoxynucleotidyl-transferase-mediated nick end labeling (TUNEL) methods.Keywords: antitumor response; cisplatin; drug delivery; gelatin nanoparticles; in vivo imaging; tumor penetration;
Co-reporter:Yuan Cheng, Shuling Yu, Xu Zhen, Xin Wang, Wei Wu, and Xiqun Jiang
ACS Applied Materials & Interfaces 2012 Volume 4(Issue 10) pp:5325
Publication Date(Web):September 28, 2012
DOI:10.1021/am3012627
In this paper, a kind of novel alginic acid nanoparticles was successfully prepared by a non-solvent-aided counterion complexation between anionic alginic acid and cationic 2,2′-(ethylenedioxy)diethylamine in aqueous solution followed by cross-linking alginic acid moiety using Ca2+. It was found that these alginic acid nanoparticles have a spherical morphology with the diameter of about 100 nm, and negatively charged surface with the zeta potential of about −30 mV. Compared to the desintegrity of un-cross-linked nanoparticles, the Ca2+-cross-linked nanoparticles maintained their integrity in the aqueous medium with the physiological pH value. Doxorubicin, a model antitumor drug, was successfully loaded into the alginic acid nanoparticles, and their in vitro and in vivo antitumor activities were evaluated. It was found that these negatively charged nanoparticles could be taken up by the cancer cells through an endocytosis mechanism. In vivo near-infrared (NIR) fluorescence imaging and biodistribution examinations showed that the alginic acid nanoparticles could be well-accumulated in the tumor site by the enhanced permeability and retention effect. In vivo antitumor examination showed that the drug-loaded nanoparticles have superior efficacy in impeding tumor growth and prolonging the lifetime of H22 tumor-bearing mice than free drug.Keywords: alginic acid; antitumor; doxorubicin; drug delivery; nanoparticles;
Co-reporter:Xue Wang, Changjing Chen, Da Huo, Hanqing Qian, Yin Ding, Yong Hu, Xiqun Jiang
Carbohydrate Polymers 2012 Volume 90(Issue 1) pp:361-369
Publication Date(Web):1 September 2012
DOI:10.1016/j.carbpol.2012.05.052
β-Cyclodextrin modified chitosan–poly(acrylic acid) nanoparticles (CS–PAACD NPs) were obtained by polymerizing acrylic acid (AA) and β-cyclodextrin (β-CD) substituted acrylic acid (AACD) in chitosan (CS) solution. These CS–PAACD NPs, characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM) as well as atomic force microscopy (AFM), were quite small in size about 40–50 nm. The size and the microstructure of these CS–PAACD NPs could be accurately controlled by changing the ration of AACD to AA. As the ratio of AACD to AA increased, the size of these NPs decreased. These as-prepared CS–PAACD NPs showed enhanced solubility for paclitaxel (PTX) in aqueous solution and exhibited a typical pH-sensitive release property for the encapsulated drug in vitro. The presence of the β-cyclodextrin inside the CS–PACD NPs greatly enhanced the ability to load hydrophobic drugs, which significantly broadened the application of CS–PAACD NPs in biomedical fields.Highlights► CS–PAACD NPs was obtained by introducing β-CD into CS–PAA nanoparticles. ► The size and the structure of CS–PAACD NPs can be controlled by varying the content of β-CD in them. ► These CS–PAACD NPs had a pH responsible property and excellent encapsulation ability to paclitaxel. ► These paclitaxel loaded CS–PAACD NPs showed high cytotoxicity against C6 glioma cells.
Co-reporter:Yuan Cheng;Shuling Yu;Jingjing Wang;Hanqing Qian;Wei Wu
Macromolecular Bioscience 2012 Volume 12( Issue 10) pp:1326-1335
Publication Date(Web):
DOI:10.1002/mabi.201200165
Co-reporter:Luzhong Zhang;Ying Lin;Yajun Zhang;Rui Chen;Zhenshu Zhu;Wei Wu
Macromolecular Bioscience 2012 Volume 12( Issue 1) pp:83-92
Publication Date(Web):
DOI:10.1002/mabi.201100197
Co-reporter:Hanqing Qian;Wei Yao;Shuling Yu;Dr. Ying Chen;Dr. Wei Wu ; Xiqun Jiang
Chemistry – An Asian Journal 2012 Volume 7( Issue 8) pp:
Publication Date(Web):
DOI:10.1002/asia.201290031
Co-reporter:Hanqing Qian;Wei Yao;Shuling Yu;Dr. Ying Chen;Dr. Wei Wu ; Xiqun Jiang
Chemistry – An Asian Journal 2012 Volume 7( Issue 8) pp:1875-1880
Publication Date(Web):
DOI:10.1002/asia.201200155
Abstract
The non-membrane-closing formation of polymer vesicles was demonstrated by the self-assembly of an amphiphilic hydrogen-bonded interpolymer complex of HPC and PAA. A dynamic-formation process that involved a nucleation and growth pathway was observed experimentally that was different from the theoretical predictions of both the membrane-closing model and the nucleation and growth model. A series of intermediate states between the solid spheres and vesicles were visually captured by the addition of an inorganic salt followed by dilution.
Co-reporter:Rui Chen, Qi Chen, Da Huo, Yin Ding, Yong Hu, Xiqun Jiang
Colloids and Surfaces B: Biointerfaces 2012 Volume 97() pp:132-137
Publication Date(Web):1 September 2012
DOI:10.1016/j.colsurfb.2012.03.027
A novel chitosan–gold (CS–Au) hybrid hydrogel was developed from chitosan and chloroauric acid in aqueous solution. Its physiochemical characteristics, including UV absorption, structure, morphology, swelling properties were studied. The CS–Au hybrid hydrogel exhibited an excellent water-absorbing property and could be applied as a drug delivery system for anticancer drug: doxorubicin (DOX) due to its high equilibrium water swelling content. The drug loading and release experiments elicited an efficient drug loading content and sustained drug release pattern. Moreover, DOX released from hydrogel which itself had no cytotoxicity was biological active similar as the free DOX, but lower cytotoxicity due to its controllable release. All proved it an ideal local drug delivery system indicating a promising potential future in medical or pharmaceutical area.Graphical abstractHighlights► We develop a novel chitosan–gold (CS–Au) hybrid hydrogel. ► Au nanoparticles work as physical cross-linking points of the hydrogel. ► The hydrogel exhibits an excellent water-absorbing and re-swelling property. ► The hydrogel can be used as a drug delivery system for doxorubicin (DOX).
Co-reporter:Eryun Yan, Yilong Fu, Xue Wang, Yin Ding, Hanqing Qian, Chi-Hwa Wang, Yong Hu and Xiqun Jiang
Journal of Materials Chemistry A 2011 vol. 21(Issue 9) pp:3147-3155
Publication Date(Web):24 Jan 2011
DOI:10.1039/C0JM03234D
Here we report the synthesis of hybrid hollow chitosan–silica nanospheres (CS–Silica NPs) with chitosan–polyacrylic acid (CS–PAA) nanoparticles as the template and doxorubicin (DOX) delivery based on CS–Silica NPs. The morphology and the microstructure of CS–Silica NPs were characterized by field emission scanning electron microscopy (FESEM) and X-ray photoelectron spectroscopy (XPS). The confocal laser scanning microscopy (CLSM) and flow cytometry experiments showed that the cellular uptake of the DOX-loaded CS–Silica NPs was time dependent. In addition, cellular internalization and intracellular distribution of DOX-loaded CS–Silica NPs indicated that the DOX was mainly distributed in the cell nucleus while the carriers were primarily located in the cytoplasm. In vivo antitumor response indicated that the DOX loaded CS–Silica hybrid hollow nanospheres exhibited superior antitumor effect over the free drugin vivo, which might be ascribable to the enhanced cellular uptake efficiency and the effective delivery of drug to the cell nucleus.
Co-reporter:Ying Lin, Luzhong Zhang, Wei Yao, Hanqing Qian, Dan Ding, Wei Wu, and Xiqun Jiang
ACS Applied Materials & Interfaces 2011 Volume 3(Issue 4) pp:995
Publication Date(Web):March 9, 2011
DOI:10.1021/am100982p
A facile approach to prepare CdSe/ZnS quantum dot-encapsulated chitosan hybrid nanospheres (CS-QD) is developed by utilizing ethanol-aided counterion complexation in aqueous solution. The obtained CS-QD hybrid nanospheres have not only the loading space provided by the chitosan spherical matrix for loading multiply QDs but also unique fluorescent properties provided by the encapsulated QDs. Moreover, these hybrid nanospheres possess good biocompatibility and optical stability in physiological environment. It is demonstrated that CS-QD hybrid nanospheres can be internalized by tumor cells and hence act as labeling agent in cell imaging by optical microscopy. In addition, CS-QD hybrid nanospheres can be used for imaging of tumor in tumor-bearing mice via intratumoral administration and can accumulate at tumor site via the blood circulation based on intravenous injection. Thus, on the one hand, chitosan nanospheres provide the protection in both colloidal and optical stability arising from QDs and offer biocompatibility. On the other hand, the encapsulated QDs light up polymer nanospheres and display the fate of polymer nanospheres in cells and bodies.Keywords: chitosan; hybrid nanospheres; imaging; quantum dots
Co-reporter:Luzhong Zhang;Ying Lin;Jingjing Wang;Wei Yao;Wei Wu
Macromolecular Rapid Communications 2011 Volume 32( Issue 6) pp:534-539
Publication Date(Web):
DOI:10.1002/marc.201000757
Co-reporter:Rui Guo;Yuan Cheng;Dan Ding;Xiaolin Li;Leyang Zhang;Baorui Liu
Macromolecular Bioscience 2011 Volume 11( Issue 6) pp:839-847
Publication Date(Web):
DOI:10.1002/mabi.201000434
Co-reporter:Chengjie Liu, Xu Zhen, Xin Wang, Wei Wu and Xiqun Jiang
Soft Matter 2011 vol. 7(Issue 24) pp:11526-11534
Publication Date(Web):25 Oct 2011
DOI:10.1039/C1SM06388J
Cellular uptake of hollow casein nanospheres was investigated by confocal microscopy, flow cytometry and transmission electron microscopy. It was found that the casein spheres could enter cellsvia a temperature- or energy-independent mechanism. Confocal microscopy and flow cytometry showed that the cellular uptake amount and velocity of the casein spheres at 4 °C were almost the same as those at 37 °C. Moreover, cellular uptake of casein spheres could not be affected by endocytosis inhibitors, suggesting that a large fraction of casein spheres enter cells in a non-endocytosis fashion. In addition, real-time confocal laser scanning microscopy observation found that the casein spheres first absorbed onto the cell membrane, and then were internalized into the cells mainly through an endocytosis-independent mechanism. Transmission electron microscopy analysis also demonstrated that the casein spheres internalized by cells were mainly distributed in the cytoplasm either at 37 or 4 °C. These findings extend the current understanding of the interactions between milk proteins and biologic systems, and offer a drug nanocarrier which itself has an extraordinary capability to penetrate cell barriers in an energy-independent fashion.
Co-reporter:Ying Chen, Hanqing Qian, Xianchuang Zheng, Xiqun Jiang, Hyuk Yu and Leyang Zhang
Soft Matter 2011 vol. 7(Issue 12) pp:5519-5523
Publication Date(Web):21 Apr 2011
DOI:10.1039/C0SM01479F
Based on the irregularly structured hydrogen bonded interpolymer complexes and their assembly, we obtained ellipsoidal polysaccharide vesicles. These vesicles not only exhibit uniform shape, but also regulate their shape and volume by transport channels like living cells.
Co-reporter:Zhiqing Mao, Wei Wu, Cheng Xie, Dunming Zhang, Xiqun Jiang
Polymer Testing 2011 Volume 30(Issue 2) pp:260-270
Publication Date(Web):April 2011
DOI:10.1016/j.polymertesting.2010.07.010
Highly lipophilic multi-walled carbon nanotubes (MWNTs) were successfully prepared by grafting PAA onto the surface of MWNT, followed by replacing carboxyl groups of PAA with octadecylamine through amidation. The improved dispersion of functionalized MWNTs and enhanced mechanical properties of nanotube/SBS composites were observed. The composite thin films with different MWNT loading prepared via spin-coating were investigated by means of atomic force microscopy (AFM) in order to study the dispersion of MWNTs in the polymer matrix. The evolution of MWNT/SBS composite thin film surface morphology with the variation of MWNT concentration is presented. When the MWNT concentration is lower than 1 wt%, the composite thin film is homogeneous. With increase of MWNT concentration, phase separation can be clearly observed. It is found that the state of aggregation of MWNTs in the polymer matrix determine the mechanical properties of the composites.
Co-reporter:Dan Ding, Zhenshu Zhu, Rutian Li, Xiaolin Li, Wei Wu, Xiqun Jiang, and Baorui Liu
ACS Nano 2011 Volume 5(Issue 4) pp:2520
Publication Date(Web):March 23, 2011
DOI:10.1021/nn102138u
The objective of this study is to investigate the anticancer efficacy of a drug delivery system comprised of gelatin hydrogel (jelly) containing cisplatin (CDDP)-loaded gelatin/poly(acrylic acid) nanoparticles by peritumoral implantation and to compare the treatment response between the implantation administration of the jelly and intravenous (i.v.) administration of the nanoparticles. It is found that the implantation of the jelly containing CDDP-loaded nanoparticles on tumor tissue exhibited significantly superior efficacy in impeding tumor growth and prolonging the lifetime of mice than that of i.v. injection of CDDP-loaded nanoparticles in a murine hepatoma H22 cancer model. An in vivo biodistribution assay performed on tumor-bearing mice demonstrated that the jelly implant caused much higher concentration and retention of CDDP in tumor and lower CDDP accumulation in nontarget organs than that of i.v. injected nanoparticles. Immunohistochemical analysis demonstrated that the nanoparticles from the jelly can be distributed in tumor tissue not only by their diffusion but also by the vasculature in the implantation region into tumor interior, enabling CDDP to efficiently reach more viable cells of tumor compared with i.v. injected nanoparticles. Thus, nanoparticles for peritumoral chemotherapy are promising for higher treatment efficacy due to increased tumor-to-normal organ drug uptake ratios and improved drug penetration in tumors.Keywords: antitumor effect; drug delivery; peritumoral chemotherapy; polymer hydrogel; polymer nanoparticles;
Co-reporter:Dan Ding;Jing Wang;Ying Chen;Wei Wu
Science China Chemistry 2011 Volume 54( Issue 2) pp:392-396
Publication Date(Web):2011 February
DOI:10.1007/s11426-010-4207-5
In this work, gelatin-poly(acrylic acid) (GEL-PAA) nanospheres with diameter of around 35 nm were prepared using a polymer-monomer (gelatin-AA) pair reaction system. These nanospheres can self-assemble into nanorods in aqueous solution at 4 °C. Based on the observation that the intermediate state of the formation of the nanorods and the facts that the self-assembly can only occur at relatively low temperature and the gelatin molecules on the outermost layer of the GEL-PAA nanospheres can be renatured to triple helix conformation, it can be rationally inferred that the hydrogen bonding and electrostatic interactions between the gelatin molecules with the triple helix structure induce the one-dimensional self-assembly of the nanospheres into nanorods.
Co-reporter:Zhenshu Zhu, Chen Xie, Qin Liu, Xu Zhen, Xianchuang Zheng, Wei Wu, Rutian Li, Yin Ding, Xiqun Jiang, Baorui Liu
Biomaterials 2011 32(35) pp: 9525-9535
Publication Date(Web):
DOI:10.1016/j.biomaterials.2011.08.072
Co-reporter:Yin Ding, Xiaochen Bian, Wei Yao, Rutian Li, Dan Ding, Yong Hu, Xiqun Jiang and Yiqiao Hu
ACS Applied Materials & Interfaces 2010 Volume 2(Issue 5) pp:1456
Publication Date(Web):April 26, 2010
DOI:10.1021/am1001019
Chitosan−gold hybrid nanospheres with varying surface zeta potentials were designed as a model system to investigate cell internalization. Gold nanoparticle was selected as optical marker to facilitate the visualization of the hybrid polymeric nanosphere internalization course and the localization in the cell by dark-field optical microscopy and transmission electron microscopy. It is found that surface potential has significant biological implications in the transmembrane efficiency, intracellular fate, and cytotoxicity of the hybrid nanospheres. Compared to those with lower surface potential, the spheres with higher surface potential show a faster cell uptake and enhance the nucleus targeting. However, too high a surface potential may destabilize the cell membrane and induce cell damage as well as cytotoxicity. These finding can help us to design suitable drug or gene nanocarriers with low cytotoxicity and high delivering ability.Keywords: cell uptake; chitosan; cytotoxicity; transmembrane ability
Co-reporter:Ying Chen, Xianchuang Zheng, Hanqing Qian, Zhiqing Mao, Dan Ding, and Xiqun Jiang
ACS Applied Materials & Interfaces 2010 Volume 2(Issue 12) pp:3532
Publication Date(Web):November 16, 2010
DOI:10.1021/am100709d
Poly(acrylic acid) (PAA) nanogels with a hollow core−porous shell structure were prepared by the direct polymerization of an acrylic acid monomer in the presence of hydroxypropylcellulose (HPC) and a cross-linking agent, N,N-methylenebisacrylamide, followed by removal of HPC from the generated HPC−PAA nanoparticles in a basic environment. The properties of PAA nanogel were characterized by dynamic light scattering, FT-IR, transmission electron microscopy, and atomic force microscopy. It is found that the nanogels have a hollow core−porous shell structure. Protein, bovine serum albumin (BSA), and an antitumor agent, doxorubicin hydrochloride, were used as model drugs to investigate their loading abilities as versatile drug-delivery vehicles. The nanogel exhibits surprisingly high loading ability to both protein and small molecular drugs. For example, the maximum BSA loading capacity of PAA nanogel can reach as high as 800% (i.e., 1 mg of nanogel can load about 8.0 mg of BSA). This high loading capacity may be related with the hollow core−porous shell structure of PAA nanogels. PAA nanogels have also shown sustained drug release properties and can cross biological barriers to deliver loaded cargo inside cells. Considering the high stability of the materials, simple and mild preparation procedure, high loading capacity, sustained-release property, and ability to protect biological agents from denaturation, PAA nanogels should be promising drug-delivery carriers for drug-delivery systems.Keywords: high capacity; hollow; nanogels; pH-sensitive; poly(acrylic acid); porous
Co-reporter:Zhenshu Zhu, Yuan Li, Xiaolin Li, Rutian Li, Zhijun Jia, Baorui Liu, Wanhua Guo, Wei Wu, Xiqun Jiang
Journal of Controlled Release 2010 Volume 142(Issue 3) pp:438-446
Publication Date(Web):19 March 2010
DOI:10.1016/j.jconrel.2009.11.002
Paclitaxel (PTX)-loaded poly(N-vinylpyrrolidone)-b-poly(ε-caprolactone) (PVP-b-PCL) nanoparticles with high drug payload were successfully prepared by a modified nano-precipitation method and characterized by transmission electron microscopy (TEM), atomic force microscopy (AFM), dynamic light scattering (DLS) and zeta potential. The satisfactory drug loading content (> 25%) and high encapsulation efficiency (> 85%) were achieved. The in vivo real-time biodistribution of PTX-loaded nanoparticles was investigated using near-infrared fluorescence (NIRF) imaging. The antitumor effect of PTX-loaded nanoparticles was evaluated, both, in vitro on three different cancer cell lines and in vivo on hepatic H22 tumor bearing mice model via intravenous administration (i.v.). It is found that PTX-loaded nanoparticles exhibit significant superior in vivo antitumor effect than the commercially available Taxol® formulation by combining the tumor volumes and survival rates measurement, intravital positron emission tomography and computed tomography (PET/CT) imaging.PTX-loaded PVP-b-PCL nanoparticles exhibit significant superior in vivo antitumor effect than the commercially available Taxol® formulation.
Co-reporter:Chengjie Liu, Wei Yao, Luzhong Zhang, Hanqing Qian, Wei Wu and Xiqun Jiang
Chemical Communications 2010 vol. 46(Issue 40) pp:7566-7568
Publication Date(Web):17 Sep 2010
DOI:10.1039/C0CC02370A
Hollow protein nanospheres are prepared in aqueous solution by molecular self-assembly, and they show extraordinary capability to penetrate cell barriers in an energy-independent fashion.
Co-reporter:Yin Ding;Yong Hu;Wei Wu
Science China Chemistry 2010 Volume 53( Issue 3) pp:479-486
Publication Date(Web):2010 March
DOI:10.1007/s11426-010-0102-3
The application of nanotechnology in medicine research has significant potential in modern biomedical research, disease diagnosis and therapy. Organic fluorophore-based detection techniques have been widely used as imaging and signal transduction tools for the detection of trace levels of analytes. The photosensitivity of the fluorophores, however, limits their application in such complex environments as living bio-systems where degradation or photobleaching occurs. Inorganic nanoparticles have unique and stable optical, electrical, magnetic and catalytic properties because of their various shapes, sizes and compositions. The potential of the nanoparticles as novel imaging agents has been studied as a possible solution to this problem. Surface modification of inorganic nanoparticles could enhance their biostability in physiological conditions and ability of targeting bioactive molecules.
Co-reporter:Yong Hu, Zhiping Jiang, Rui Chen, Wei Wu and Xiqun Jiang
Biomacromolecules 2010 Volume 11(Issue 2) pp:
Publication Date(Web):January 14, 2010
DOI:10.1021/bm901211r
The nonenzymatic and enzymatic degradation behaviors of the poly(vinyl pyrrolidone)-poly(ε-caprolactone) (PVP-PCL) diblock copolymers micelles in aqueous solution were investigated by dynamic light scattering (DLS), size exclusion chromatography (SEC), and high performance liquid chromatography (HPLC), and the morphology variation of these micelles in the degradation procedure were inspected by transmission electronic microscopy (TEM). It is found that the enzymatic degradation of PVP-PCL micelles is much faster and the degradation rate of PVP-PCL micelles is proportional to the enzyme concentration for a given micelles’ concentration. However, in the nonenzymatic case, the degradation of PVP-PCL micelles is quite slow under neutral condition and fast in acidic or basic medium. Interestingly, morphology transformation from spheres to a necklace and rod-like nanostructure was observed during the degradation procedure under basic condition. This shape reconstruction of PVP-PCL nanoparticles in the degradation process opens a new window to fabricate hierarchical supramolecular structures.
Co-reporter:Rui Guo, Leyang Zhang, Hanqing Qian, Rutian Li, Xiqun Jiang and Baorui Liu
Langmuir 2010 Volume 26(Issue 8) pp:5428-5434
Publication Date(Web):January 22, 2010
DOI:10.1021/la903893n
Multifunctional nanocarriers based on chitosan/gold nanorod (CS-AuNR) hybrid nanospheres have been successfully fabricated by a simple nonsolvent-aided counterion complexation method. Anticancer drug cisplatin was subsequently loaded into the obtained hybrid nanospheres, utilizing the loading space provided by the chitosan spherical matrix. In vitro cell experiments demonstrated that the CS-AuNR hybrid nanospheres can not only be utilized as contrast agents for real-time cell imaging but also serve as a near-infrared (NIR) thermotherapy nanodevice to achieve irradiation-induced cancer cell death owing to the unique optical properties endowed by the encapsulated gold nanorods. In addition, an effective attack on the cancer cells by the loaded anticancer drug cisplatin has also been observed, rendering the obtained nanocarriers an all-in-one system possessing drug delivery, cell imaging, and photothermal therapy functionalities.
Co-reporter:Yong Hu;Qi Chen;Yin Ding;Rutian Li;Baorui Liu
Advanced Materials 2009 Volume 21( Issue 36) pp:3639-3643
Publication Date(Web):
DOI:10.1002/adma.200803682
Co-reporter:Yin Ding;Qi Chen;Hanqing Qian;Ying Chen;Wei Wu;Yong Hu
Macromolecular Bioscience 2009 Volume 9( Issue 12) pp:1272-1280
Publication Date(Web):
DOI:10.1002/mabi.200900245
Co-reporter:ChangJing Chen;Yu Deng;ErYun Yan;Yong Hu
Science Bulletin 2009 Volume 54( Issue 18) pp:3127-3136
Publication Date(Web):2009 September
DOI:10.1007/s11434-009-0259-3
In this work, the preparation of chitosan-poly(acrylic acid)-calcium phosphate hybrid nanoparticles (CS-PAA-CaP NP) based on the mineralization of calcium phosphate (CaP) on the surface of chitosan-poly (acrylic acid) nanoparticles (CS-PAA NPs) was reported. CS-PAA-CaP NPs were achieved by directly adding ammonia to the aqueous solution of CS-PAA nanoparticles or by thermal decomposition of urea in the aqueous solution of CS-PAA nanoparticles, resulting in the mineralization of CaP on the surface of CS-PAA NPs. Through these two routes, especially using urea as a pH-regulator, the precipitation of CS-PAA NPs, a common occurrence in basic environment, was avoided. The size, morphology and ingredient of CS-PAA-CaP hybrid nanoparticles were characterized by dynamic light scattering (DLS), transmission electron microscope (TEM), scanning electron microscope (SEM), thermogravimetry analysis (TGA) and X-ray diffractometer (XRD). When urea was used as the pH regulator to facilitate the mineralization during the thermal urea decomposition procedure, regular CS-PAA-CaP hybrid nanoparticles with a porosity-structural CaP shells and 400–600 nm size were obtained. TGA result revealed that the hybrid NPs contained approximately 23% inorganic component, which was consistent with the ratio of starting materials. The XRD spectra of hybrid nanoparticles indicated that dicalcium phosphate (DCP: CaHPO4) crystal was a dominant component of mineralization. The porous structure of the CS-PAA-CaP hybrid NPs might be greatly useful in pharmaceutical and other medical applications.
Co-reporter:Wei Wu, Rutian Li, Xiaochen Bian, Zhenshu Zhu, Dan Ding, Xiaolin Li, Zhijun Jia, Xiqun Jiang and Yiqiao Hu
ACS Nano 2009 Volume 3(Issue 9) pp:2740
Publication Date(Web):August 24, 2009
DOI:10.1021/nn9005686
A multiwalled carbon nanotube (MWNT)-based drug delivery system was developed by covalently combining carbon nanotubes with the antitumor agent 10-hydroxycamptothecin (HCPT) using hydrophilic diaminotriethylene glycol as the spacer between nanotube and drug moieties. The surface functionalizations of the nanotube were carried out by enrichment of carboxylic groups with optimized oxidization treatment, followed by covalently linking hydrophilic diaminotriethylene glycol via amidation reaction, and then HCPT was chemically attached to carbon nanotubes through a cleavable ester linkage. It is demonstrated that the obtained MWNT−HCPT conjugates are superior in antitumor activity both in vitro and in vivo to clinical HCPT formulation. In vivo single photon emission computed tomography (SPECT) imaging and ex vivo gamma scintillation counting analyses reveal that MWNT−HCPT conjugates have relatively long blood circulation and high drug accumulation in the tumor site. These properties together with the enhanced cell uptake and multivalent presentation of HCPT on a single nanotube benefit substantially the antitumor effects and would boost significantly the applications of carbon nanotubes in the biomedicine field.Keywords: 10-hydroxycamptothecin; antitumor performance; biodistribution; carbon nanotubes; drug delivery;
Co-reporter:Ying Chen, Dan Ding, Zhiqing Mao, Yafeng He, Yong Hu, Wei Wu and Xiqun Jiang
Biomacromolecules 2008 Volume 9(Issue 10) pp:
Publication Date(Web):August 30, 2008
DOI:10.1021/bm800484e
To develop a novel type of semi-IPN particles using biocompatible materials, hydroxypropylcellulose-poly(acrylic acid) (HPC-PAA) particles with semi-interpenetrating polymer network structure and a porosity-structural surface were prepared by direct polymerization of acrylic acid monomer in the reaction system comprised of HPC and AA monomer and N,N′-methylenebisacrylamide (MBAAm). The properties of HPC-PAA gel particles were characterized by dynamic light scattering, FT-IR, transmission electron microscopy, and atomic force microscope. It is found that the formation of HPC-PAA gel particles is driven by the hydrogen bonding interaction between proton-donating PAA and proton-accepting HPC. These HPC-PAA gel particles exhibit thermo and pH dual-responsive behaviors. Depending on the chemical composition and the degree of cross-linking, the thermo-responsive property of HPC-PAA gel particles can be shifted from the UCST to the LCST property, and particle sizes can be changed from 100 to 1 μm in a controllable way. Successful loading of the gel particles with oxaliplatin, a hydrophilic antitumor drug, was achieved by take advantage of the complex interaction between the platinum atom of oxaliplatin and the carboxylic group of PAA in the gel particles. In vitro cytotoxicity assay indicates that the oxalipatin-loaded HPC-PAA gel particles have high anticancer activity. Considering the good biosafety, simple and mild preparation strategy and tunable size as well as the stimuli-responsive properties, the HPC-PAA gel particles should be a promising candidate for the drug delivery system.
Co-reporter:L. Zhang;M. Yang;R. Guo;X. Jiang;B. Liu
Advanced Materials 2007 Volume 19(Issue 19) pp:2988-2992
Publication Date(Web):5 SEP 2007
DOI:10.1002/adma.200601817
Thermo and pH dual-responsive nanoparticles encapsulating an anti-cancer drug (paclitaxel) were assembled from a diblock copolymer comprised of a hydrophilic poly(N-isopropylacrylamide-co-acrylic acid) block and a hydrophobic polycaprolactone block. These nanoparticles aggregated at body temperature under a slightly acidic pH of 6.9 (see figure), and a faster drug release was found to be associated with higher temperature and lower pH, both of which are advantageous for tumor-targeted anti-caner drug delivery.
Co-reporter:Leyang Zhang, Mi Yang, Qin Wang, Yuan Li, Rui Guo, Xiqun Jiang, Changzheng Yang, Baorui Liu
Journal of Controlled Release 2007 Volume 119(Issue 2) pp:153-162
Publication Date(Web):1 June 2007
DOI:10.1016/j.jconrel.2007.02.013
10-Hydroxycamptothecin (HCPT) loaded nanoparticles made from poly(caprolactone-co-lactide)-b–PEG–b-poly(caprolactone-co-lactide) (PCLLA–PEG–PCLLA) block copolymer, were prepared by a novel two-step nanoprecipitation method using an interior-chemistry strategy. The satisfactory drug loading content (> 13%) as well as high encapsulation efficiency (> 85%) was achieved. Cytotoxicity test indicated that the HCPT-loaded nanoparticles had enhanced in vitro cytotoxicity compared to free drug. Progressively, in vivo antitumor activity and HCPT biodistribution in sarcoma-180 (S-180) bearing mice after intravenous injection of the HCPT-loaded nanoparticles show that HCPT-loaded nanoparticles exhibited superior in vivo antitumor effect and remarkably different biodistribution than the commercially available HCPT injection.
Co-reporter:Xiaochen Shen;Leyang Zhang Dr. ;Yong Hu Dr.;Jian Guo Dr.
Angewandte Chemie International Edition 2007 Volume 46(Issue 37) pp:
Publication Date(Web):8 AUG 2007
DOI:10.1002/anie.200701368
Inside out and back again: A novel nanogel composed of two biocompatible components, namely chitosan and ethylenediaminetetraacetic acid, is presented and shows novel surface switching of both composition and charge in response to pH changes in the medium (see picture). The pH-dependent surface switch of this nanogel is fully reversible and the particle integrity is maintained in the entire pH range owing to the gel nature of the system.
Co-reporter:Xiaochen Shen;Leyang Zhang Dr. ;Yong Hu Dr.;Jian Guo Dr.
Angewandte Chemie 2007 Volume 119(Issue 37) pp:
Publication Date(Web):8 AUG 2007
DOI:10.1002/ange.200701368
Wie eine Wendejacke: Ein neuartiges Nanogel aus den beiden biokompatiblen Komponenten Chitosan und Ethylendiamintetraessigsäure schaltet die Zusammensetzung und Ladung seiner Oberfläche auf Änderungen des pH-Werts hin (siehe Bild). Durch die Geleigenschaften des Systems ist dieser Prozess komplett reversibel, und die Partikel bleiben über den gesamten pH-Bereich stabil.
Co-reporter:Jie Cai;Zhijun Chen;Yun Liu;Li Xu;Rongshi Cheng;Zhiqing Mao
Journal of Applied Polymer Science 2006 Volume 102(Issue 4) pp:3118-3122
Publication Date(Web):29 AUG 2006
DOI:10.1002/app.24045
The random copolymers (HO-P(St-r-MMA)-COOH) of styrene (St) and methyl methacrylate (MMA) with hydroxyl group at one end and carboxyl group at another end were synthesized by nitroxide-mediated living radical polymerization initiated by 4,4′-azobis(4-cyanovaleric acid) (ACVA) and 4-hydroxyl-2,2,6,6–tetramethylpiperidineoxyl (TEMPO-OH). The experimental results have shown that all synthesized copolymers have narrow molecular weight distribution. The conversion of monomers and the molecular weight of copolymer increase with polymerization time. Thus, a copolymerization mechanism containing living radical polymerization is suggested. The use of this method permits the copolymer with two functional chain ends and controllable molecular weight as well as low molecular weight distribution. X-ray photoelectron spectroscopy result shows that the synthesized copolymers can be tethered on the surface of silicon wafer through the reaction between the hydroxyl end of the copolymer and native oxide layer on the wafer. In addition, an organic/inorganic hybrid surface has achieved by treating copolymer tethered Si-substrates with SiCl4 vapor. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 3118–3122, 2006
Co-reporter:Yong Hu;Yonghua Yang;Ying Chen;Qi Chen
Macromolecular Bioscience 2005 Volume 5(Issue 10) pp:993-1000
Publication Date(Web):6 OCT 2005
DOI:10.1002/mabi.200500098
Summary: We report here a study on the microstructure formation process of polymeric nanoparticles based on polyelectrolyte complexes. When polyanion poly(acrylic acid) (PAA) was dropped into polycation chitosan (CS) solution, CS-PAA nanoparticles with diverse microstructure would be formed under different experimental conditions. The microstructure of CS-PAA nanoparticles changed from solid spherical nanoparticles to core-shell separative ones and turned back to solid spherical ones with the variation of preparation conditions. The influence of molecular weight of CS and PAA, shell cross-linking, dropping temperature on the size, stability and morphology of CS-PAA nanoparticles were also studied. The nanoparticle size was affected by the molecular weight of CS and PAA, the ratio of amino group to carboxyl group (na/nc) and the incubation temperature as well. The shell-cross-linking provides a means to stabilize these nanoparticles. These nanoparticles can encapsulate plasmid DNA very well, which makes them have great potential in gene delivery.
Co-reporter:Dunming Zhang;Changzheng Yang
Journal of Applied Polymer Science 2005 Volume 98(Issue 1) pp:347-352
Publication Date(Web):20 JUL 2005
DOI:10.1002/app.22090
Stable and translucent polydimethylsiloxane nanolatices in a water–aminoethanol (AE) system were prepared by the emulsion polymerization of octamethylcyclotetrasiloxane (D4) with nonionic polyoxyethylene alcohol ethers and polyoxyethylene aryl ether as surfactants and with KOH as an initiator. The effects of the AE concentration on the emulsion polymerization rate (Rp) of D4 and the physical properties of the resultant nanolatices were investigated. Increasing the AE concentration in the reaction mixture dramatically increased the emulsion Rp value of D4, and the kinetics of the D4 emulsion polymerization in this system were consistent with the Morgan–Kaler theory of microemulsion polymerization. When the AE concentration in the emulsion increased, the transparency value of the resultant emulsion increased, and the size of the droplets in the resultant nanolatices decreased. In addition, the molecular weight of the polysiloxane in the resultant emulsion also increased with the increase in the AE concentration in the reaction mixture. A nanolatex prepared by the emulsion polymerization of 0.98M D4 with 185 g/L AE had a transparency value of 80.9% and a mean diameter of 59.5 nm. The morphology of polysiloxane nanolatices cured with (N,N-diethylaminomethyl)-triethoxysilane was observed with transmission electron microscopy, and the size of the globular particles was consistent with that obtained by dynamic light scattering. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 98: 347–352, 2005
Co-reporter:Y. Hu;X. Jiang;Y. Ding;Q. Chen;C. Z. Yang
Advanced Materials 2004 Volume 16(Issue 11) pp:
Publication Date(Web):17 JUN 2004
DOI:10.1002/adma.200306579
Co-reporter:Leyang Zhang, Yong Hu, Xiqun Jiang, Changzheng Yang, Wei Lu, Yong Hua Yang
Journal of Controlled Release 2004 Volume 96(Issue 1) pp:135-148
Publication Date(Web):16 April 2004
DOI:10.1016/j.jconrel.2004.01.010
Triblock copolymers of poly(caprolactone-co-lactide)-b-PEG-b-poly(caprolactone-co-lactide) (PCLLA-PEG-PCLLA) were synthesized by ring opening copolymerization of caprolactone and lactide in the presence of poly(ethylene glycol) (PEG). With such triblock copolymers, PCLLA-PEG-PCLLA nanoparticles entrapping 10-hydroxycamptothecin-10,20-diisobutyl dicarbonate (HCPT-1), a derivative of the antitumor drug 10-hydroxycamptothecin (HCPT), were prepared by nano-precipitation method and characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM) and atomic force microscopy (AFM). The investigations on drug loading, in vitro release and body distribution in mice after intravenous (i.v.) administration were also carried out. It is found that the obtained nanoparticles showed smooth surface and spherical shape with the controllable size in the range of 70–180 nm, and drug loading content varied from 3.3% to 7.0% depending on the copolymer composition and preparation conditions. The in vitro release behavior exhibited a sustaining release manner and was affected by particle size as well as copolymer composition. The results of body distribution study in mice show that the blood concentration of HCPT-1 could be maintained for a long period and the tissue distribution was influenced by the particle size to some extent. These results suggest that the PCLLA-PEG-PCLLA nanoparticles seem to be a promising delivery system for poorly soluble antitumor drugs or their derivatives.
Co-reporter:Yuan Wang;Zhijun Chen;Yan Feng;Changzheng Yang;Mu Wang
Journal of Applied Polymer Science 2004 Volume 91(Issue 3) pp:1842-1847
Publication Date(Web):5 DEC 2003
DOI:10.1002/app.13364
The random copolymers of styrene (St) and 4-vinylpyridine (4-VP) with hydroxyl end group and low polydispersities were synthesized by nitroxide-mediated living radical polymerization initiated by azobisisobutyronitrile (AIBN) and 4-hydroxyl-2,2,6,6–tetramethylpiperidine-oxyl (TEMPO-OH). The experimental results have shown that all synthesized copolymers have narrow molecular weight distribution. The conversion of monomers and the molecular weight of copolymer increased with polymerization time. The copolymerization rate is affected by molar ratios of HTEMPO to AIBN. 1H-Nuclear magnetic resonance spectra shows that one end of copolymers was capped by TEMPO-OH moiety. The use of this method permits the copolymer with hydroxyl chain end and controllable molecular weight and molecular weight distribution. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 91: 1842–1847, 2004
Co-reporter:Yin Ding;Yong Hu Dr. ;Leyang Zhang;Changzheng Yang
Angewandte Chemie 2004 Volume 116(Issue 46) pp:
Publication Date(Web):23 NOV 2004
DOI:10.1002/ange.200460408
Magnetische Nanohohlkugeln aus Fe3O4 und einem Polymer (siehe Bild) wurden erhalten, indem Fe3O4-Nanopartikel zu einer Lösung von Polymer-Monomer-Paaren gegeben wurden, die aus einem kationischen Polymer (Chitosan) und einem anionischen Monomer (Acrylsäure) bestanden. Anschließend wurde die Acrylsäure polymerisiert, und nach der Polymerisation wurde das Chitosan selektiv vernetzt.
Co-reporter:Yin Ding;Yong Hu Dr. ;Leyang Zhang;Changzheng Yang
Angewandte Chemie International Edition 2004 Volume 43(Issue 46) pp:
Publication Date(Web):23 NOV 2004
DOI:10.1002/anie.200460408
Magnetic hollow Fe3O4–polymer hybrid nanospheres (see figure) were prepared by adding Fe3O4 nanoparticles to an aqueous solution of polymer–monomer pairs composed of a cationic polymer (chitosan) and an anionic monomer (acrylic acid), followed by polymerization of acrylic acid and selective crosslinking of chitosan at the end of the polymerization.
Co-reporter:Dong Xiang;Qundong Shen;Suyang Zhang
Journal of Applied Polymer Science 2003 Volume 88(Issue 5) pp:1350-1356
Publication Date(Web):19 FEB 2003
DOI:10.1002/app.11841
A novel alternating copolymer, poly{[2,5-di(2-(2-ethoxy ethoxy)ethoxy)-1,4-phenylene vinylene]-alt-1,4-[phenylene vinylene]}, has been synthesized through the Wittig condensation as electroluminescent material. In this copolymer, one component is phenylene vinylene with flexible oligo(ethylene oxide) side chain that facilitates ion transportation and phase miscibility between nonpolar and polar part of composite luminescent layer, and another is a rigid phenylene vinylene moiety to improve luminescent quantum efficiency and tune color. The copolymer shows good solubility and thermal stability for device fabrication compared to poly(phpeylene vinylene)(PPV). The band gap value of copolymer is between those of corresponding homopolymers, which indicates that alternating copolymerization is a suitable way to obtain luminescent polymer with desired band gap. The maximum wavelength of photoluminescence of copolymer is 539 nm (yellowish-green). The HOMO and LUMO energy levels obtained by cyclic voltammetry measurement indicate that the electron injection ability of copolymer has been greatly improved compared with that of the PPV. A more balanced carrier injection and higher quantum efficiency are proved by electroluminescent properties of corresponding light-emitting devices. The turn-on voltage of LEC device (ITO/copolymer + PEO + LiClO4/Al) is found to be 2.3 V, with current comparative to LED (ITO/copolymer/Al) at 9.5 V. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 88: 1350–1356, 2003
Co-reporter:Zhijun Chen;Jie Cai;Changzheng Yang
Journal of Applied Polymer Science 2002 Volume 86(Issue 11) pp:2687-2692
Publication Date(Web):24 SEP 2002
DOI:10.1002/app.11236
The poly(4-vinylpyridine) with hydroxyl end group and narrow polydispersity was synthesized by polymerization of 4-vinylpyridine by the use of nitroxide initiator based on 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl and azobisisobutyronitrile. The effects of different initiator amounts and reaction time on polymerization rate, molecular weight, and molecular weight distribution of the poly(4-vinylpyridine) were investigated at bulk polymerization. The experimental results have shown that the polymerization of 4-vinylpyridine is a controlled living free-radical polymerization; the molecular weight is proportional to reaction time; and the molecular weight and molecular weight distribution are affected by molar ratios of [4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl]/[azobisisobutyronitrile]. By varying the ratio of 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl to azobisisobutyronitrile, the poly(4-vinylpyridine) with narrow polydispersity can be obtained. X-ray photoelectron spectroscopy results show that the synthesized poly(4-vinylpyridine) can be tethered on the surface of silicon wafer through the reaction between hydroxyl end of poly(4-vinylpyridine) and native silicon oxide layer on the wafer surface. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 2687–2692, 2002
Co-reporter:Chengjie Liu, Wei Yao, Luzhong Zhang, Hanqing Qian, Wei Wu and Xiqun Jiang
Chemical Communications 2010 - vol. 46(Issue 40) pp:NaN7568-7568
Publication Date(Web):2010/09/17
DOI:10.1039/C0CC02370A
Hollow protein nanospheres are prepared in aqueous solution by molecular self-assembly, and they show extraordinary capability to penetrate cell barriers in an energy-independent fashion.
Co-reporter:Ying Lin, Sanxi Wang, Yajun Zhang, Jiangang Gao, Liu Hong, Xin Wang, Wei Wu and Xiqun Jiang
Journal of Materials Chemistry A 2015 - vol. 3(Issue 28) pp:NaN5710-5710
Publication Date(Web):2015/05/28
DOI:10.1039/C5TB00593K
Superparamagnetic iron oxide nanoparticles encapsulated in hydrophilic chitosan nanospheres were prepared by nonsolvent-aided counterion complexation completely in an aqueous solution. The T2 relaxation of these hybrid nanospheres in vitro and in vivo was investigated. It was found that the molar transverse relaxivity rate r2 of hybrid nanospheres highly depends upon the payload of iron oxide nanoparticles within hybrid nanospheres. Compared to free iron oxide nanoparticles, the molar transverse relaxivity rate, r2 of hybrid nanospheres shows an approximately 8-fold increase and reaches the maximum of 533 Fe mM−1 s−1. Such a high r2 value is probably associated with the clustering effect of iron oxide nanoparticles, which are confined in the chitosan nanospheres. The in vivo magnetic resonance imaging (MRI) demonstrates that the hybrid nanospheres shorten transverse relaxation time, T2 and significantly decrease the signal intensity of the tumor area, giving rise to high contrast tumor MR imaging at a relatively low dose.
Co-reporter:Jing Wang, Kejian Yao, Chongzhi Wang, Chuanbing Tang and Xiqun Jiang
Journal of Materials Chemistry A 2013 - vol. 1(Issue 17) pp:NaN2332-2332
Publication Date(Web):2013/03/05
DOI:10.1039/C3TB20100G
Well-defined amphiphilic poly(ethylene glycol) and poly(dehydroabietic ethyl methacrylate) block copolymers (PEG-b-PDAEMA) were prepared by atom transfer radical polymerization. The methacrylate block contains a characteristic hydrophobic, biocompatible and economical dehydroabietic moiety. PEG-b-PDAEMA block copolymer micellar nanoparticles loaded with piperlongumine (PLGM) were successfully prepared by a nanoprecipitation method. In vitro and in vivo behaviors of these nanoparticles were thoroughly examined by a set of characterization techniques. Confocal laser scanning microscopy study revealed that these nanoparticles could be well taken up by cancer cells. In vivo near-infrared fluorescence imaging showed that the PLGM-loaded nanoparticles effectively targeted the tumor site by the enhanced permeability and retention (EPR) effect in H22 tumor-bearing mice. The in vivo antitumor examination found that PLGM-loaded nanoparticles exhibited superior efficacy in impeding the tumor growth compared to the commercially available Taxol® and free PLGM formulation. The changes in body weights and blood biochemical profiles were also compared to investigate the safety of PLGM and PEG-b-PDAEMA nanoparticle drug delivery system.
Co-reporter:Eryun Yan, Yilong Fu, Xue Wang, Yin Ding, Hanqing Qian, Chi-Hwa Wang, Yong Hu and Xiqun Jiang
Journal of Materials Chemistry A 2011 - vol. 21(Issue 9) pp:NaN3155-3155
Publication Date(Web):2011/01/24
DOI:10.1039/C0JM03234D
Here we report the synthesis of hybrid hollow chitosan–silica nanospheres (CS–Silica NPs) with chitosan–polyacrylic acid (CS–PAA) nanoparticles as the template and doxorubicin (DOX) delivery based on CS–Silica NPs. The morphology and the microstructure of CS–Silica NPs were characterized by field emission scanning electron microscopy (FESEM) and X-ray photoelectron spectroscopy (XPS). The confocal laser scanning microscopy (CLSM) and flow cytometry experiments showed that the cellular uptake of the DOX-loaded CS–Silica NPs was time dependent. In addition, cellular internalization and intracellular distribution of DOX-loaded CS–Silica NPs indicated that the DOX was mainly distributed in the cell nucleus while the carriers were primarily located in the cytoplasm. In vivo antitumor response indicated that the DOX loaded CS–Silica hybrid hollow nanospheres exhibited superior antitumor effect over the free drugin vivo, which might be ascribable to the enhanced cellular uptake efficiency and the effective delivery of drug to the cell nucleus.
Co-reporter:Ying Lin, Wei Yao, Yuan Cheng, Hanqing Qian, Xin Wang, Yin Ding, Wei Wu and Xiqun Jiang
Journal of Materials Chemistry A 2012 - vol. 22(Issue 12) pp:NaN5693-5693
Publication Date(Web):2012/02/10
DOI:10.1039/C2JM15133B
ZnFe2O4 nanoparticles were tightly packed and encapsulated in chitosan nanospheres by a nonsolvent-aided counterion complexation method. The obtained hybrid nanospheres exhibited not only the superparamagnetic properties provided by pure ZnFe2O4 nanoparticles but also a much higher r2 relaxivity value than separate ZnFe2O4 nanoparticles, representing an approximately 3 to 16 fold increase. This was attributed to the high ZnFe2O4 payload and ZnFe2O4 nanoparticle clustering effect in the core of the nanospheres. The MR images generated in vivo demonstrated that the hybrid nanospheres showed an excellent contrast in T2 weighted MRI and a high MRI sensitivity in the tumor sites for both passive and active targeting samples. In addition, the biodistribution analysis revealed that the obtained hybrid nanospheres could accumulate at tumor sites via passive and active targeting strategies.
Co-reporter:Wei Yao, Hanqing Qian, Jialiang Zhang, Wei Wu and Xiqun Jiang
Chemical Communications 2012 - vol. 48(Issue 56) pp:NaN7081-7081
Publication Date(Web):2012/05/24
DOI:10.1039/C2CC32387G
A polymeric multivesicular system was created by hydrating a film. This system underwent multifusion events and eventually evolved into giant multilamellar vesicles with extremely thick walls. The semi-permeable wall and large size make these vesicles suitable for encapsulating living cells.
Co-reporter:Rui Chen, Xianchuang Zheng, Hangqing Qian, Xin Wang, Jing Wang and Xiqun Jiang
Biomaterials Science (2013-Present) 2013 - vol. 1(Issue 3) pp:NaN293-293
Publication Date(Web):2012/11/06
DOI:10.1039/C2BM00138A
Motivated by the enhanced cytotoxicity of some chemotherapeutic agents at temperature rise, multifunctional chitosan nanospheres which co-carried gold nanorods and cisplatin were prepared. These hybrid nanospheres were characterized by dynamic light scattering, zeta potential, UV-Vis absorption spectra and transmission electron microscopy. It was demonstrated that these 120 nm-sized hybrid nanospheres could be selectively accumulated at the tumor site with about 11% injection dose per g of tumor, and produced local hyperthermia to an average temperature of 49 °C in tumor tissue after near-IR irradiation for 10 min. Due to the enhanced cytotoxicity of cisplatin at elevated temperatures, cisplatin-loaded hybrid nanospheres showed about one-second lower IC50 values than hybrid nanospheres alone in vitro and almost complete tumor growth inhibition in vivo. Compared with chemotherapy or photothermal treatment alone, the combined photothermal therapy and chemotherapy had a significantly synergistic effect and improved the therapeutic efficacy, which was supported by immunofluorescence staining and in vivo apoptosis imaging.
Co-reporter:Jing Wang, Shanmei Yuan, Yajun Zhang, Wei Wu, Yong Hu and Xiqun Jiang
Biomaterials Science (2013-Present) 2016 - vol. 4(Issue 9) pp:NaN1360-1360
Publication Date(Web):2016/07/18
DOI:10.1039/C6BM00201C
Zwitterionic poly(carboxybetaine) (PCB), poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) and non-ionic poly(ethylene glycol) (PEG), which have similar degrees of polymerization, were grafted to branched polyethyleneimine (PEI) to generate PCB-grafted PEI (PEI-PCB), PMPC-grafted PEI (PEI-PMPC) and PEG-grafted PEI (PEI-PEG) copolymers, respectively. These grafted PEI copolymers with almost the same grafting number were coated on the surface of 110 nm bovine serum albumin-poly(N-3-acrylamidophenylboronic acid) (BSA-PAPBA) nanoparticles to make a comparison of the surface decoration effect on the biodistribution of nanoparticles. Compared to the nanoparticles without surface decoration, surface decoration with the copolymers significantly prolonged the circulation time of BSA-PAPBA nanoparticles, leading to remarkable enhancement of tumor uptake of the nanoparticles. The drug accumulation at the tumor site reached more than 10% injected dose per gram of tumor. Among them, the PEI-PMPC-decorated nanoparticles exhibited the best performance in tumor accumulation and anticancer ability. Thus, these surface-decorated nanoparticles may serve as a strong candidate for high tumor accumulation of drug delivery systems.
Co-reporter:Hanqing Qian, Xin Wang, Kangjun Yuan, Chen Xie, Wei Wu, Xiqun Jiang and Lijiang Hu
Biomaterials Science (2013-Present) 2014 - vol. 2(Issue 2) pp:NaN232-232
Publication Date(Web):2013/10/07
DOI:10.1039/C3BM60176E
A methacrylation strategy was used to functionalize carboxymethyl cellulose and prepare redox-sensitive cellulose nanogels which contained disulfide bonds. Dynamic light scattering, zeta potential and electron microscopy were utilized to characterize these nanogels. It was found that these nanogels had a spherical morphology with a diameter of about 192 nm, and negative surface potential. These redox-sensitive nanogels were stable against high salt concentration but de-integrated in the reducing environment containing glutathione. When doxorubicin (DOX) was loaded into the nanogels, a high drug loading content (36%) and a high encapsulation efficiency (83%) were achieved. Confocal laser scanning microscopy and co-localization images showed that DOX-loaded nanogels were internalized by the cancer cells through endocytosis and the DOX could be delivered into the nucleus. Near-infrared fluorescence imaging biodistribution examination indicated that the nanogels could passively target to the tumor area by the EPR effect and had a significantly prolonged circulation time. In vivo antitumor evaluation found that DOX-loaded nanogels exhibited a significantly superior antitumor effect than the free DOX by combining the tumor volume measurement and the examination of cell apoptosis and proliferation in tumor tissues.
Co-reporter:Xikuang Yao, Qiwen Zhu, Cheng Li, Kangjun Yuan, Rui Che, Peng Zhang, Chenchen Yang, Wei Lu, Wei Wu and Xiqun Jiang
Journal of Materials Chemistry A 2017 - vol. 5(Issue 4) pp:NaN848-848
Publication Date(Web):2016/12/22
DOI:10.1039/C6TB02863B
Conjugation of sugars to antitumor drugs can facilitate drug binding to tumor cells and the saccharide motifs of bleomycins (BLMs) play a crucial role in tumor-seeking. Here, we synthesized BLM monosaccharide, carbamoylmannose, and subsequently prepared carbamoylmannose decorated platinum-incorporating supramolecular nanoparticles formed through the host–guest complexation of poly(N-vinylpyrrolidone) and poly(aspartic acid). The targeting effects of carbamoylmannose decorated supramolecular nanoparticles in various cancer cells and tumor-bearing mice were investigated. It was found that the nanoparticles showed a specific in vitro and in vivo carbamoylmannose-mediated cellular uptake and drug delivery. The cellular uptake of the nanoparticles followed the receptor-mediated endocytosis mechanism in cancer cells but not in healthy cells. In a murine hepatic H22 tumor model, it was demonstrated that the carbamoylmannose moiety increased the plasma concentration, tumor targeting ability and tumor penetration of the nanoparticles, leading to high tumor accumulation and superior antitumor efficacy. This carbamoylmannose molecule may bring an opportunity to design and construct inexpensive but highly efficient drug and gene delivery systems in the future.
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![Propanoic acid, 2-[(ethoxythioxomethyl)thio]-, 2-propyn-1-yl ester](/data/chemimg/3781800/1293989-84-0.png)
![Propanoic acid, 2-[(ethoxythioxomethyl)thio]-, 2-propyn-1-yl ester](/data/chemimg/3781800/1293989-84-0_b.png)
![3-Pyridinecarboxaldehyde, 6-benzo[b]thien-2-yl-](/data/chemimg/3781800/1314880-65-3.png)
![3-Pyridinecarboxaldehyde, 6-benzo[b]thien-2-yl-](/data/chemimg/3781800/1314880-65-3_b.png)
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4-phenylene-1,2-ethenediyl]](http://img.cochemist.com/ccimg/302800/302790-69-8.png)
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4-phenylene-1,2-ethenediyl]](http://img.cochemist.com/ccimg/302800/302790-69-8_b.png)
![Benzene, 1,4-bis[2-(2-ethoxyethoxy)ethoxy]-](http://img.cochemist.com/ccimg/161500/161470-80-0.png)
![Benzene, 1,4-bis[2-(2-ethoxyethoxy)ethoxy]-](http://img.cochemist.com/ccimg/161500/161470-80-0_b.png)
![Tricyclo[3.3.1.13,7]decaneacetic acid](http://img.cochemist.com/ccimg/42900/42862-38-4.png)
![Tricyclo[3.3.1.13,7]decaneacetic acid](http://img.cochemist.com/ccimg/42900/42862-38-4_b.png)
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