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用于高效基因递送的生物可还原的以倍半硅氧烷为核的星形聚阳离子

Bioreducible POSS-cored star-shaped polycation for efficient gene delivery.

作者信息

Yang Yan-Yu, Wang Xing, Hu Yang, Hu Hao, Wu De-Cheng, Xu Fu-Jian

机构信息

State Key Laboratory of Chemical Resource Engineering, Key Laboratory of Carbon Fiber and Functional Polymers, Ministry of Education, Beijing Laboratory of Biomedical Materials, College of Materials Science & Engineering, Beijing University of Chemical Technology , Beijing 100029, China.

出版信息

ACS Appl Mater Interfaces. 2014 Jan 22;6(2):1044-52. doi: 10.1021/am404585d. Epub 2013 Dec 9.

DOI:10.1021/am404585d
PMID:24299237
Abstract

The bioreducible star-shaped gene vector (POSS-(SS-PDMAEMA)8) with well-defined structure and relatively narrow molecular weight distribution was synthesized via atom transfer radical polymerization (ATRP) of (2-dimethylamino)ethyl methacrylate (DMAEMA) from a polyhedral oligomeric silsesquioxane (POSS) macroinitiator. POSS-(SS-PDMAEMA)8 was composed of a biocompatible POSS core and eight disulfide-linked PDMAEMA arms, wherein the PDMAEMA chain length could be adjusted by controlling polymerization time. POSS-(SS-PDMAEMA)8 can effectively bind pDNA into uniform nanocomplexes with appropriate particle size and zeta potential. The incorporation of disulfide bridges gave the POSS-(SS-PDMAEMA)8 material facile bioreducibility. In comparison with POSS-(PDMAEMA)8 without disulfide linkage, POSS-(SS-PDMAEMA)8 exhibited much lower cytotoxicity and substantially higher transfection efficiency. The present work would provide useful information for the design of new POSS-based drug/gene carriers.

摘要

通过从多面体低聚倍半硅氧烷(POSS)大分子引发剂引发甲基丙烯酸(2-二甲基氨基)乙酯(DMAEMA)的原子转移自由基聚合(ATRP),合成了结构明确且分子量分布相对较窄的可生物还原星形基因载体(POSS-(SS-PDMAEMA)8)。POSS-(SS-PDMAEMA)8由生物相容性的POSS核心和八个二硫键连接的PDMAEMA臂组成,其中PDMAEMA链长可通过控制聚合时间进行调节。POSS-(SS-PDMAEMA)8能够有效地将pDNA结合成具有合适粒径和zeta电位的均匀纳米复合物。二硫键的引入赋予了POSS-(SS-PDMAEMA)8材料简便的生物还原性。与没有二硫键连接的POSS-(PDMAEMA)8相比,POSS-(SS-PDMAEMA)8表现出低得多的细胞毒性和实质上更高的转染效率。本工作将为新型POSS基药物/基因载体的设计提供有用信息。

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