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学科主题: 药学
题名:
Self-assembly cationic nanoparticles based on cholesterol-grafted bioreducible poly(amidoamine) for siRNA delivery
作者: Chen, Cheng-Jun; Wang, Jian-Cheng; Zhao, En-Yu; Gao, Ling-Yan; Feng, Qiang; Liu, Xiao-Yan; Zhao, Zhi-Xia; Ma, Xiao-Fei; Hou, Wen-Jie; Zhang, Liang-Ren; Lu, Wan-Liang; Zhang, Qiang
关键词: Cholesterol-grafted bioreducible poly(amidoamine) ; Grafting degree ; Self-assembly cationic nanoparticle ; siRNA delivery ; Tumor therapy
刊名: BIOMATERIALS
发表日期: 2013-07-01
DOI: 10.1016/j.biomaterials.2013.03.056
卷: 34, 期:21, 页:5303-5316
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]: ENDOTHELIAL GROWTH-FACTOR ; GENE-TRANSFER PROPERTIES ; LUNG-CANCER CELLS ; DISULFIDE LINKAGES ; RNA INTERFERENCE ; AMINO-GROUPS ; CO-DELIVERY ; THERAPY ; TRANSFECTION ; POLYMERS
英文摘要:

In this study, a series of bioreducible poly(amidoamine)s grafting different percentages of cholesterol (rPAA-Ch14: 14%, rPAA-Ch29: 29%, rPAA-Ch57: 57% and rPAA-Ch87: 87%) was synthesized and used for siRNA delivery. These amphiphilic polymers were able to self-assemble into cationic nanoparticles in aqueous solution at low concentrations. The nanoparticle formation was evidenced via cryo-transmission electron microscope (Cryo-TEM) and dynamic light scattering analysis. The average hydrodynamic size of rPAA-Ch blank nanoparticles was about 80-160 nm with zeta potential of 50 -60 mV. Also, the effects of different percentages of cholesterol grafted onto rPAA on physicochemical characteristics, in vitro cytotoxicity, cellular uptake, VEGF gene silencing efficacy and translocation mechanism of rPAA-Ch/siRNA complexes were investigated. The results showed that rPAA-Ch57 polymer was not only able to form stable nanocomplexes and possess high cell uptake, but also to exhibit the best in vitro VEGF gene silencing efficacy and the best in vivo tumor growth inhibition effect when it was formulated with VEGF-siRNA. Moreover, the observations of confocal laser scanning microscope (CLSM) and the study of cholesterol competitive inhibition demonstrated that endosomal/lysosomal escape and cytoplasmic dissociation of rPAA-Ch57/siRNA complexes were dependent on the "proton sponge effect" and disulfide cleavage, following internalization with cholesterol-related endocytosis pathway and subsequent transportion into endosomes/lysosomes. These findings indicated that the rPAA-Ch57 polymer should be a promising and potent carrier for siRNA delivery. (C) 2013 Elsevier Ltd. All rights reserved.

语种: 英语
所属项目编号: 81273455 ; 81072597 ; 2013CB932501 ; 2009CB930300 ; 7112089 ; BMU20110268 ; BMU20110263
项目资助者: NSFC ; National Basic Research Program of China (973 Program) ; Beijing NSF project ; Ministry of Education
WOS记录号: WOS:000319630000040
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/57922
Appears in Collections:北京大学药学院_期刊论文

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

Recommended Citation:
Chen, Cheng-Jun,Wang, Jian-Cheng,Zhao, En-Yu,et al. Self-assembly cationic nanoparticles based on cholesterol-grafted bioreducible poly(amidoamine) for siRNA delivery[J]. BIOMATERIALS,2013,34(21):5303-5316.
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