BIOMATERIALS
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2014
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IF 8.312
Tinghui Yin,Ping Wang,Jingguo Li,Yiru Wang,Bowen Zheng,Rongqin Zheng,Du Cheng,Xintao Shuai
Drug resistance is a big problem in systemic chemotherapy of hepatocellular carcinoma (HCC), and nanomedicines loaded with both chemotherapeutic agents (e.g. paclitaxel, PTX) and siRNA's targeting antiapoptosis genes (e.g. BCL-2) possess the advantages to simultaneously overcome the efflux pump-mediated drug resistance and antiapoptosis-related drug resistance. However, tumor-penetrating drug delivery with this type of nanomedicines is extremely difficult due to their relatively big size compared to the single drug-loaded nanomedicines. Aiming at address this problem, US-responsive nanobubbles encapsulating both anti-cancer drug paclitaxel (PTX) and siRNA (PTX–NBs/siRNA) for HCC treatment were developed by hetero-assembly of polymeric micelles and liposomes in the present study. Utilizing an external low-frequency US force imposed to the tumor site, effective tumor-penetrating codelivery of siRNA and PTX was achieved via tail vein injection of PTX–NBs/siRNA into nude mice bearing human HepG2 xerografts. Consequently, the PTX treatment-inducible antiapoptosis in HepG2 cells was effectively suppressed by the codelivered siRNA targeting an antiapoptosis gene (BCL-2 siRNA) during chemotherapy. Owing to the synergistic anti-cancer effect of two therapeutic agents, tumor growth was completely inhibited using low-dose PTX in animal study. Our results highlight the great potential of this type of US-responsive hetero-assemblies carrying both anti-cancer drug and siRNA as an effective nanomedicinal system for HCC therapy.
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高影响因子
Materials Science & Engineering C-Materials for Biological Applications
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2014
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IF 2.736
Hui-Kang Yang,Li-Ming Zhang
For the development of biomimetic carriers for stimuli-sensitive delivery of anticancer drugs, a novel amphiphilic glycopolypeptide conjugate containing the disulfide bond was prepared for the first time by the ring-opening polymerization of benzyl glutamate N -carboxy anhydride in the presence of (propargyl carbamate)ethyl dithio ethylamine and then click conjugation with α-azido dextran. Its structure was characterized by Fourier-transform infrared spectroscopy and nuclear magnetic resonance analyses. Owing to its amphiphilic nature, such a conjugate could self assemble into nanosize micelles in aqueous medium, as confirmed by fluorometry, transmission electron microscopy and dynamic light scattering. For the resultant micelles, it was found to encapsulate poorly water-soluble anticancer drug (methotrexate, MTX) with the loading efficiency of 45.2%. By the in vitro drug release tests, the release rate of encapsulated MTX was observed to be accelerated significantly in the presence of 10 mM 1,4-dithio-DL-threitol (DTT), analogous to the intracellular redox potential.
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JOURNAL OF APPLIED POLYMER SCIENCE
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2013
·Vol. 131
·期 1
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IF 1.395
Lili Yu,Lin Yao,Jing You,Yihui Guo,Liyan Yang
A crosslinked amphiphilic copolymer [poly(ethylene glycol) (PEG)–poly(methyl methacrylate) (PMMA)–ethylene glycol dimethacrylate (EGDM)] composed of PMMA, PEG, and crosslinking units (EGDM) was synthesized by atom transfer radical polymerization to develop micelles as carriers for hydrophobic drugs. By adjusting the molar ratio of methyl methacrylate and EGDM, three block copolymer samples (P0, P1, and P2) were prepared. The measurement of gel permeation chromatography and 1 H-NMR indicated the formation of crosslinked structures for P1 and P2. Fluorescence spectroscopy measurement indicated that PEG–PMMA–EGDM could self-assemble to form micelles, and the critical micelle concentration values of the crosslinked polymer were lower than those of linear ones. The prepared PEG–PMMA–EGDM micelles were used to load doxorubicin (DOX). The drug-loading efficiencies of P1 and P2 were higher than that of P0 because the crosslinking units enhanced the micelles' stability. With increasing drug-loading contents, DOX release from the micelles in vitro was decreased, and in the crosslinked formulations, the release rate was also slower. An in vitro release study indicated that DOX release from the micelles for the linear samples was faster than that for crosslinked micelles. The drug feeding amount increased and resulted in an increase in the drug-loading content, and the loading efficiency decreased. These PEG–PMMA–EGDM micelles did not show toxicity in vitro and could reduce the cytotoxicity of DOX in the micelles; this suggested that they are good candidates as stable drug carriers. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131 , 39623.
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AICHE JOURNAL
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2014
·Vol. 61
·期 1
·35-45
·
IF 2.581
Feng Xu,Jing-Wen Xu,Bi-Xia Zhang,Luo Yan-Ling
Novel tri-armed star polystyrene-block-poly(N-isopropylacrylamide) block copolymers with trimesic acid as central molecules were synthesized by successive two-step atom transfer radical polymerization, and confirmed by Fourier-transform infrared spectra, 1 H nuclear magnetic resonance, and laser light scattering gel chromatography system. The copolymers could self-assemble into spherical core-shell micelles in aqueous media independent on drug loading. Physicochemical properties of the blank and drug-loaded micelles were examined by surface tension, fluorescence spectroscopy, UV-vis, transmission electron microscope, and dynamic light scattering measurements. The copolymer micelles exhibited thermo-triggered phase transition, with low critical solution temperature of 33.7 and 34.6°C, varying with copolymer compositions. The critical aggregate concentrations were 11.62 and 47.61 mg L −1 , and hydrodynamic diameters from 200 to 220 nm. Water-insoluble 10-hydroxycamptothecine was encapsulated into the micelle aggregates to investigate the change in the resulting physicochemical parameters, thermo-triggered in vitro drug release, and the applicability as drug targeting release carriers. MTT assays were carried out to uncover cytotoxicity of the newly developed micelle-based drug formulations. © 2014 American Institute of Chemical Engineers AIChE J , 61: 35–45, 2015
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International Journal of Nanomedicine
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2013
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IF 3.463
Xiao-juan Hu,Yang Liu,Xiao-feng Zhou,Qiao-ling Zhu,Yong-yan Bei,Ben-gang You,Chun-ge Zhang,Wei-liang Chen,Zhou-li Wang,Ai-jun Zhu,Xue-nong Zhang,Yu-jiang Fan
Novel amphiphilic chitosan derivatives (N-caprinoyl-N-trimethyl chitosan [CA-TMC]) were synthesized by grafting the hydrophobic moiety caprinoyl (CA) and hydrophilic moiety trimethyl chitosan to prepare carriers with good compatibility for poorly soluble drugs. Based on self-assembly, CA-TMC can form micelles with sizes ranging from 136 nm to 212 nm. The critical aggregation concentration increased from 0.6 mg • L −1 to 88 mg • L −1 with decrease in the degree of CA substitution. Osthole (OST) could be easily encapsulated into the CA-TMC micelles. The highest entrapment efficiency and drug loading of OST-loaded CA-TMC micelles(OST/CA-TMC) were 79.1% and 19.1%, respectively. The antitumor efficacy results show that OST/CA-TMC micelles have significant antitumor activity on Hela and MCF-7 cells, with a 50% of cell growth inhibition (IC50) of 35.8 and 46.7 μg. mL −1 , respectively. Cell apoptosis was the main effect on cell death of Hela and MCF-7 cells after OST administration. The blank micelles did not affect apoptosis or cell death of Hela and MCF-7 cells. The fluorescence imaging results indicated that OST/CA-TMC micelles could be easily uptaken by Hela and MCF-7 cells and could localize in the cell nuclei. These findings suggest that CA-TMC micelles are promising carriers for OST delivery in cancer therapy.
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高影响因子
LANGMUIR
·
2015
·
IF 4.457
Lichao Sun,Hanying Zhao
Lipid membrane fusion is a fundamental process in nature. In the fusion process two distinct bilayers merge the hydrophobic layers, and an interconnected structure is produced. In this research, the fusion of polymer membrane self-assembled by cleaved pinned micelles is investigated. Disulfide-tethered poly(tert-butyl acrylate-block-styrene) diblock copolymer brushes on the surfaces of silica particles were prepared by the “grafting to” or “grafting from” method. In acetone, the diblock copolymer brushes self-assemble into pinned micelles. Upon cleavage from the surfaces of the silica particles with n-tributylphosphine, the pinned micelles self-assemble into vesicles. In the meanwhile, thiol groups at the ends of the block copolymer brushes were produced in the cleavage reaction. Because of the oxidation of the thiol groups and the formation of the disulfide bonds, the vesicle structures are fused into bigger hollow structures and fiber-like structures. The further fusion of the fiber-like structures results in precipitation of the polymer from the solution.
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Materials Science & Engineering C-Materials for Biological Applications
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2017
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IF 4.164
Xiaolong Tang,Shuping Zhou,Xinrong Tao,Jian Wang,Fangyu Wang,Yong Liang
Delivery of taxane-based chemotherapeutics including Docetaxel (DTX) by conventional polymeric micelles still suffers from insufficient stability and rapid premature release during the circulation, which limits their targeting and anticancer efficiency. To conquer these challenges, we developed a novel DTX-loaded Pi-Pi stacking-stabilized dendritic polymeric micelle for targeted therapy of liver cancer. This dendritic polymeric micelle, referred to DPM-DTX-cRGD, was self-assembled from DTX and biodegradable dendritic block copolymers Poly(amidoamine)-poly(γ-benzyl- l -Glutamate)- b -polyethylene glycol-cRGD (PAM-PBLG- b -PEG-cRGD). DPM-DTX-cRGD held robust stability due to its covalent dendritic structure and would load abundant DTX with excellent retention via Pi-Pi stacking between DTX and the aromatic groups of the PBLG segments. The cellular uptake studies demonstrated that the cRGD-conjugated dendritic polymeric micelle (DPM) exhibited much higher cellular uptake in human liver cancer HepG2 cells than non-targeted DPM. The MTT assay also confirmed that DPM-DTX-cRGD caused much greater cytotoxicity than non-targeted DPM-DTX and a clinically available DTX formulation (Taxotere®). Therefore, this DPM-DTX-cRGD provides a novel attractive approach for targeted therapy of liver cancer.
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高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2015
·Vol. 16
·期 12
·28146-28155
·
IF 2.862
Qing You,Yan Zhang,Huan Wang,Hongfu Fan,Jianping Guo,Ming Li
Wormlike micelles are typically formed by mixing cationic and anionic surfactants because of attractive interactions in oppositely charged head-groups. The structural transitions of wormlike micelles triggered by pH in ionic liquids composed ofN-alkyl-N-methylpyrrolidinium bromide-based ILs (ionic liquids) and anthranilic acid were investigated. These structures were found responsible for the variations in flow properties identified by rheology and dynamic light scattering, and account for the structures observed with cryogenic transmission electron microscopy (Cryo-TEM). High-viscosity, shear-thinning behavior, and Maxwell-type dynamic rheology shown by the system at certain pH values suggested that spherical micelles grow into entangled wormlike micelles. Light scattering profiles also supported the notion of pH-sensitive microstructural transitions in the solution. Cryo-TEM images confirmed the presence of spherical micelles in the low-viscosity sample and entangled wormlike micelles in the peak viscosity sample. Nuclear magnetic resonance spectroscopy analysis revealed that the pH sensitivity of ionic liquid systems originated from the pH-dependent binding ability of anthranilic acid to the cationic headgroup of ionic liquids.Keywords:pH-sensitive;wormlike micelles;rheology;morphological variation;formation mechanism
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高影响因子
BIOMACROMOLECULES
·
2024
·
IF 5.5
Panpan Zhang,Leitao Zhang,Zhihao Wang,Qiuli Cheng,Wenlan Wu,Junbo Li,Gaofeng Liang,Ravin Narain
Bioorthogonal reactions present a promising strategy for minimizing off-target toxicity in cancer chemotherapy, yet a dependable nanoplatform is urgently required. Here, we have fabricated an acid-responsive polymer micelle for the specific delivery and activation of the prodrug within tumor cells through Ru catalyst-mediated bioorthogonal reactions. The decomposition of micelles, triggered by the cleavage of the hydrazone bond in the acidic lysosomal environment, facilitated the concurrent release of Alloc-DOX and the Ru catalyst within the cells. Subsequently, the uncaging process of Alloc-DOX was demonstrated to be induced by the high levels of glutathione within tumor cells. Notably, the limited glutathione inside normal cells prevented the conversion of Alloc-DOX into active DOX, thereby minimizing the toxicity toward normal cells. In tumor-bearing mice, this nanoplatform exhibited enhanced efficacy in tumor suppression while minimizing off-target toxicity. Our study provides an innovative approach for in situ drug activation that combines safety and effectiveness in cancer chemotherapy.
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BIOMATERIALS
·
2011
·
IF 7.883
Jing Li,Meirong Huo,Jing Wang,Jianping Zhou,Jumah M. Mohammad,Yinlong Zhang,Qinnv Zhu,Ayman Y. Waddad,Qiang Zhang
A targeted intracellular delivery system of paclitaxel (PTX) was successfully developed based on redox-sensitive hyaluronic acid-deoxycholic acid (HA-ss-DOCA) conjugates. The conjugates self-assembled into nano-size micelles in aqueous media and exhibited excellent drug-loading capacities (34.1%) and entrapment efficiency (93.2%) for PTX. HA-ss-DOCA micelles were sufficiently stable at simulated normal physiologic condition but fast disassembled in the presence of 20 m m reducing agent, glutathione . In vitro drug release studies showed that the PTX-loaded HA-ss-DOCA micelles accomplished rapid drug release under reducing condition. Intracellular release of fluorescent probe nile red indicated that HA-ss-DOCA micelles provide an effective approach for rapid transport of cargo into the cytoplasm. Enhanced cytotoxicity of PTX-loaded HA-ss-DOCA micelles further confirmed that the sensitive micelles are more potent for intracellular drug delivery as compared to the insensitive control. Based on flow cytometry and confocal microscopic analyses, observations revealed that HA-ss-DOCA micelles were taken up to human breast adenocarcinoma cells (MDA-MB-231) via HA-receptor mediated endocytosis . In vivo investigation of micelles in tumor-bearing mice confirmed that HA-ss-DOCA micelles possessed much higher tumor targeting capacity than the insensitive control. These results suggest that redox-sensitive HA-ss-DOCA micelles hold great potential as targeted intracellular delivery carriers of lipophilic anticancer drugs.
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EUROPEAN POLYMER JOURNAL
·
2024
·
IF 5.8
Longxin Lin,Yaling Zheng,Caixia Huang,Lanlan Cai,Hua Zhang,Wen Xu,Xiaoying Wang,Wei Xu
Oral drug delivery with tumor-targeting treatment persists as a challenge. In this study, a mixed polymeric micelle (PM) delivery system was designed to overcome the barriers to oral administration for tumor-targeting delivery of paclitaxel (PTX) for breast cancer treatment. D-α-Tocopheryl polyethylene glycol 1000 succinate-modified carboxymethyl chitosan-rhein (TCR) conjugate and Biotin-polyethylene glycol 2000-Biotin (BPB) conjugate were mixed to form TCR-BPB PMs. The particle size and polydispersity index of optimized PTX-loaded TCR-BPB PMs (PTX/TCR-BPB PMs) was 195.90 ± 7.63 nm and 0.08 ± 0.00, with a drug-loading capacity of 41.94 ± 2.47 %. In simulated gastroenteric fluid and blood environments, the PMs presented a sustained-release manner. PTX/TCR-BPB PMs were taken up by Caco-2 and 4T1 cells and displayed strong cytotoxicity in a time- and concentration-dependent manner. PTX/TCR-BPB PMs significantly improved intestinal absorption of PTX. The pharmacokinetics, tissue distribution, and in vivo imaging indicated that PTX/TCR-BPB PMs could enhance oral bioavailability of PTX, prolong the retention time of PTX in the blood, and enhance PTX tumor-targeting ability. PTX/TCR-BPB PMs enhance the antitumor efficacy of PTX and reduce its toxicity in normal organs. Therefore, TCR-BPB PMs are expected to serve as delivery carriers for the oral and tumor-targeting delivery of hydrophobic antitumor drugs.
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JOURNAL OF MOLECULAR LIQUIDS
·
2024
·
IF 5.3
Wenjing Zhang,Shengfeng Ye,Zhaolan Zhai,Dan Wang,Shibin Shang,Zhanqian Song
Fluorescent nanomaterials have drawn considerable attentions due to their high fluorescence sensitivity, excellent signal stability and tunable luminescent properties. A bio-based aggregation-induced emission (AIE) surfactant (Sodium 4-(tetraphenylstyrene)maleate, MPA-TPE-Na) was prepared from rosin, which showed typical AIE characteristic, obvious solvatochromism and a large Stokes shift (>100 nm). AIE viscoelastic solutions were further prepared by complexing MPA-TPE-Na and cetyltrimethylammonium bromide (CTAB) through coordinating aggregation and their microstructure, fluorescence properties and viscoelasticities were investigated. The aggregates in the viscoelastic solutions were wormlike micelles. As the concentration of MPA-TPE-Na increased, the fluorescence intensity of the viscoelastic solutions increased, and their viscosity increased at first and then decreased. The fluorescence emission intensity of the viscoelastic solutions was barely affected by the change in pH. But reducing the pH could increase its viscosity. This system can specifically recognize Fe 3+ without any organic solvent and has anti-interference ability. The present work provided a bio-based fluorescent nanomaterial and verified the feasibility of preparing aqueous AIE nanomaterials by modifying AIE groups with rosin skeleton.
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