pH响应的PEG化基因传递体系  

pH-Responsive PEGylated Gene Delivery System

作　　者：刘亚杰[1] 张鹏[1] 杜建委 王幽香[1] 

机构地区：[1]浙江大学高分子合成与功能构造教育部重点实验室,高分子科学与工程学系,杭州310027

出　　处：《高等学校化学学报》2016年第5期1003-1009,共7页Chemical Journal of Chinese Universities

基　　金：国家自然科学基金(批准号:21474087,51273177)资助

摘　　要：制备了苯甲酰亚胺键偶联的聚乙二醇化(PEG化)聚乙烯亚胺(m PEG-CH=N-PEI),并以还原无p H响应特性m PEG-PEI作为对照.研究结果表明,PEG链段的引入并未影响聚乙烯亚胺与脱氧核糖核酸(DNA)分子的缔合,形成了尺寸为80 nm,表面电位约为10 m V的基因超分子组装体,具有很好的生理盐稳定性.在模拟溶酶体的酸性环境下,苯甲酰亚胺键有效断裂,显示出很好的p H响应特性.Hep G2细胞培养结果表明,由于PEG链段有效屏蔽了组装体表面的正电荷,PEG化组装体的细胞毒性和内吞效率显著降低,但溶酶体酸性条件使苯甲酰亚胺键断裂,有利于组装体逃离溶酶体,因此m PEG-CH=N-PEI依然具有很高的基因转染效率,实现了基因载体细胞外稳定传递、细胞内响应解离并高效转染的功能.The p H-sensitive polyethylene glycol-grafted polyethylenimine（ m PEG-CH=N-PEI） was synthesized via benzoic imine linker according to the acidic environment of endosomal. The corresponding stable PEGylated polyethylenimine（ m PEG-PEI） without p H-sensitivity was synthesized as control. The results showed that both PEGylated polycations could condense DNA into tight spherical nanoparticles about 80 nm in size and 10 m V in ξ-potential,which showed excellent stability under physiological conditions. The benzoic imine linkers were easily cleaved under the p H of 5,which was similar with the endosomal p H. Human hepatoblastoma cell line（ Hep G2） cell culture results indicated that the cytotoxicity and cellular uptake efficiency of both PEGylated gene nanoparticles decreased remarkably because of the shielding effect of PEG shell. Due to the cleavage of benzoic imine linker at acidic environment of endosomal,the PEG shell of m PEG-CH=N-PEI/DNA polyplexes was detachable and lead to quick endosomal escape. So m PEGCH=N-PEI/DNA polyplexes showed higher gene expression than the m PEG-PEI/DNA polyplexes. Based on these results,we concluded that PEGylated polyplexes via benzoic imine linkers showed high extracellular stability,intracellular DNA release and effective gene transfection.

关 键 词：非病毒基因载体 聚乙烯亚胺 PH响应 聚乙二醇化 

分 类 号：O631.3[理学—高分子化学] Q782[理学—化学]