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Self-assembly nanomicelles based on cationic mPEG-PLA-b-Polyarginine(R-15) triblock copolymer for siRNA delivery
Zhao, Zhi-Xia; Gao, Shan-Yun; Wang, Jian-Cheng; Chen, Cheng-Jun; Zhao, En-Yu; Hou, Wen-Jie; Feng, Qiang; Gao, Ling-Yan; Liu, Xiao-Yan; Zhang, Liang-Ren; Zhang, Qiang
关键词Biodegradable copolymer Polyarginine Micelleplex siRNA delivery Nanocarrier Tumor therapy
刊名BIOMATERIALS
2012-10-01
DOI10.1016/j.biomaterials.2012.05.067
33期:28页:6793-6807
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Engineering, Biomedical ; Materials Science, Biomaterials
资助者NSFC ; Beijing NSF ; National Basic Research Program of China (973 Program) ; Program for New Drug RD ; Ministry of Education ; NSFC ; Beijing NSF ; National Basic Research Program of China (973 Program) ; Program for New Drug RD ; Ministry of Education
研究领域[WOS]Engineering ; Materials Science
关键词[WOS]SMALL INTERFERING RNAS ; GENE DELIVERY ; IN-VITRO ; MULTIDRUG-RESISTANCE ; NANOPARTICLES ; CARRIER ; CYTOTOXICITY ; MICELLES ; POLYETHYLENIMINE ; ACTIVATION
英文摘要

Due to the absence of safe and effective carriers for in vivo delivery, the applications of small interference RNA (siRNA) in clinic for therapeutic purposes have been limited. In this study, a biodegradable amphiphilic tri-block copolymer (mPEG(2000)-PLA(3000)-b-R-15) composed of monomethoxy poly(ethylene glycol), poly(d,l-lactide) and polyarginine was synthesized and further self-assembled to cationic polymeric nanomicelles for in vivo siRNA delivery, with an average diameter of 54.30 +/- 3.48 nm and a zeta potential of approximately 34.8 +/- 1.77 mV. The chemical structures of the copolymers were well characterized by H-1 NMR spectroscopy and FT-IR spectra. In vitro cytotoxicity and hemolysis assays demonstrated that the polymeric nanomicelles showed greater cell viability and haemocompatibility than those of polyethyleneimine (PEI) or R-15 peptide. In vitro experiments demonstrated that EGFR targeted siRNA formulated in micelleplexes exhibited approximately 65% inhibition of EGFR expression on MCF-7 cells in a sequence-specific manner, which was comparable to Lipofectamine (TM) 2000. The results of intravenous administration showed Micelleplex/EGFR-siRNA significantly inhibited tumor growth in nude mice xenografted MCF-7 tumors, with a remarkable inhibition of EGFR expression. Furthermore, no positive activation of the innate immune responses and no significant body weight loss was observed during treatment suggested that this polymeric micelle delivery system is non-toxic. In conclusion, the present nanomicelles based on cationic mPEG(2000)-PLA(3000)-b-R-15 copolymer would be a safe and efficient nanocarrier for in vivo delivery of therapeutic siRNA. (C) 2012 Elsevier Ltd. All rights reserved.

语种英语
所属项目编号81072597 ; 7112089 ; 2007CB935800 ; 2009CB930300 ; 2009ZX09310-001 ; BMU20110268 ; BMU20110263
资助者NSFC ; Beijing NSF ; National Basic Research Program of China (973 Program) ; Program for New Drug RD ; Ministry of Education ; NSFC ; Beijing NSF ; National Basic Research Program of China (973 Program) ; Program for New Drug RD ; Ministry of Education
WOS记录号WOS:000308270000021
引用统计
被引频次:62[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/60450
专题北京大学药学院_药剂学系
作者单位Peking Univ, Dept Pharmaceut, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
推荐引用方式
GB/T 7714
Zhao, Zhi-Xia,Gao, Shan-Yun,Wang, Jian-Cheng,et al. Self-assembly nanomicelles based on cationic mPEG-PLA-b-Polyarginine(R-15) triblock copolymer for siRNA delivery[J]. BIOMATERIALS,2012,33(28):6793-6807.
APA Zhao, Zhi-Xia.,Gao, Shan-Yun.,Wang, Jian-Cheng.,Chen, Cheng-Jun.,Zhao, En-Yu.,...&Zhang, Qiang.(2012).Self-assembly nanomicelles based on cationic mPEG-PLA-b-Polyarginine(R-15) triblock copolymer for siRNA delivery.BIOMATERIALS,33(28),6793-6807.
MLA Zhao, Zhi-Xia,et al."Self-assembly nanomicelles based on cationic mPEG-PLA-b-Polyarginine(R-15) triblock copolymer for siRNA delivery".BIOMATERIALS 33.28(2012):6793-6807.
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