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Contribution of cholesterol moieties attached on MPEG-b-PCL-b-PLL to the cell uptake, endosomal escape and gene knockdown of the micelleplexes of siRNA

文献类型:期刊论文

作者Qi, Ruo-gu1,2; Wu, Su-hong1,2; Wang, Yu1; Chen, Jie1; Xie, Zhi-gang1; Huang, Yu-bin1; Jing, Xia-bin1
刊名CHINESE JOURNAL OF POLYMER SCIENCE
出版日期2013-06-01
卷号31期号:6页码:912-923
关键词Amphiphilic Copolymer Cholesterol Endosome Escape Micelleplex Sirna Delivery
ISSN号0256-7679
DOI10.1007/s10118-013-1288-6
英文摘要To further enhance the transfection efficiency of a micelleplex system based on monomethoxy poly(ethylene glycol)-block-poly(E >-caprolactone)-block-poly(L-lysine) (MPEG-b-PCL-b-PLL), cholesterol (Chol) moieties are attached to the E >-termini of PLL segments to obtain MPEG-b-PCL-b-PLL/Chol. The structure and morphology of the copolymer are studied by H-1-NMR, TEM and DLS (dynamic light scattering). The cytotoxicity, cell uptake, endosomal release and mRNA knockdown are studied by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay, flow cytometry, CLSM (confocal laser scanning microscopy) and RT-PCR (real-time polymerase chain reaction). The results show that compared to their precursor MPEG-b-PCL-b-PLL, the cholesterol-grafted copolymer shows significantly lower toxicity, more rapid cellular endocytosis and endosome escape, and consequently displays enhanced siRNA transfection efficiency even at a lower N/P ratio. These improvements are ascribed to enhanced interaction of the cholesterol moieties with both cellular membrane and endosomal membrane. Moreover, effect of the PLL block length is examined. The final conclusion is that long enough PLL segments and incorporation of proper fraction of cholesterol onto the PLL segments benefit the enhancement of siRNA transfection efficiency.
语种英语
WOS记录号WOS:000317985500008
出版者SPRINGER
源URL[http://ir.iccas.ac.cn/handle/121111/46607]  
专题中国科学院化学研究所
通讯作者Jing, Xia-bin
作者单位1.Chinese Acad Sci, Changchun Inst Appl Chem, State Key Lab Polymer Phys & Chem, Changchun 130022, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
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Qi, Ruo-gu,Wu, Su-hong,Wang, Yu,et al. Contribution of cholesterol moieties attached on MPEG-b-PCL-b-PLL to the cell uptake, endosomal escape and gene knockdown of the micelleplexes of siRNA[J]. CHINESE JOURNAL OF POLYMER SCIENCE,2013,31(6):912-923.
APA Qi, Ruo-gu.,Wu, Su-hong.,Wang, Yu.,Chen, Jie.,Xie, Zhi-gang.,...&Jing, Xia-bin.(2013).Contribution of cholesterol moieties attached on MPEG-b-PCL-b-PLL to the cell uptake, endosomal escape and gene knockdown of the micelleplexes of siRNA.CHINESE JOURNAL OF POLYMER SCIENCE,31(6),912-923.
MLA Qi, Ruo-gu,et al."Contribution of cholesterol moieties attached on MPEG-b-PCL-b-PLL to the cell uptake, endosomal escape and gene knockdown of the micelleplexes of siRNA".CHINESE JOURNAL OF POLYMER SCIENCE 31.6(2013):912-923.

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来源:化学研究所

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