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Self-assembly cationic nanoparticles based on cholesterol-grafted bioreducible poly(amidoamine) for siRNA delivery
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
2013-07-01
DOI10.1016/j.biomaterials.2013.03.056
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
WOS记录号WOS:000319630000040
项目编号81273455 ; 81072597 ; 2013CB932501 ; 2009CB930300 ; 7112089 ; BMU20110268 ; BMU20110263
资助机构NSFC ; National Basic Research Program of China (973 Program) ; Beijing NSF project ; Ministry of Education
引用统计
被引频次:55[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/400002259/57922
专题北京大学药学院
北京大学药学院_药物化学系
北京大学药学院_药剂学系
作者单位Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
推荐引用方式
GB/T 7714
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.
APA Chen, Cheng-Jun.,Wang, Jian-Cheng.,Zhao, En-Yu.,Gao, Ling-Yan.,Feng, Qiang.,...&Zhang, Qiang.(2013).Self-assembly cationic nanoparticles based on cholesterol-grafted bioreducible poly(amidoamine) for siRNA delivery.BIOMATERIALS,34(21),5303-5316.
MLA Chen, Cheng-Jun,et al."Self-assembly cationic nanoparticles based on cholesterol-grafted bioreducible poly(amidoamine) for siRNA delivery".BIOMATERIALS 34.21(2013):5303-5316.
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