Yang Yan-Yu, Wang Xing, Hu Yang, Hu Hao, Wu De-Cheng, Xu Fu-Jian
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.
ACS Appl Mater Interfaces. 2014 Jan 22;6(2):1044-52. doi: 10.1021/am404585d. Epub 2013 Dec 9.
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.
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。