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学科主题: 药学
题名:
Self-assembly nanomicelles based on cationic mPEG-PLA-b-Polyarginine(R-15) triblock copolymer for siRNA delivery
作者: 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
发表日期: 2012-10-01
DOI: 10.1016/j.biomaterials.2012.05.067
卷: 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
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
项目资助者: 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
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/60450
Appears in Collections:北京大学药学院_药剂学系_期刊论文

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作者单位: Peking Univ, Dept Pharmaceut, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China

Recommended Citation:
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.
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