基于多组分反应合成具有双功能基团的高效聚合物基因载体
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- 英文论文题名：Endosomal-Escape Polymers Based on Multicomponent Reaction-Synthesized Monomers Integrating Alkyl and Imidazolyl Moieties for Efficient Gene Delivery
- 论文作者：查增仕 ; 李军杰 ; 葛治伸
- 英文论文作者：Zengshi Zha ; Junjie Li ; Zhishen Ge ; CAS Key Laboratory of Soft Matter Chemistry ; Department of Polymer Science and Engineering ; University of Science and Technology of China
- 年：2016
- 作者机构：中科院软物质化学重点实验室高分子科学与工程系中国科学技术大学;
- 论文关键词：多组分反应 ; PDMAEMA ; 内涵体逃逸 ; 基因载体
- 会议召开时间：2016-07-01
- 会议录名称：中国化学会第30届学术年会摘要集-第三十八分会：纳米生物效应与纳米药物化学
- 语种：中文
- 分类号：TQ460.1
- 学会代码：ZGHY
- 会议名称：中国化学会第30届学术年会-第三十八分会 ; 纳米生物效应与纳米药物化学
- 会议地点：中国辽宁大连
- 主办单位：中国化学会
- 学会名称：中国化学会
- 页数：1
- 文件大小：127k
- 原文格式：D
- 会议级别：全国
摘要
高效的内涵体逃逸往往决定了纳米医药的最终治疗效率,尤其是对在溶酶体中易于降解的核酸或蛋白质药物。为了实现更加高效的内涵体逃逸效率,我们利用Passerini多组分反应将具有高效质子海绵效应的分子和易于与内涵体膜结合的长链烷基结合到一个单体中,聚合后得到的聚合物表现出了非常高效的内涵体逃逸效率。将该聚合物引入到常规阳离子聚合物基因载体,聚甲基丙烯酸N,N-二甲氨基乙酯(PDMAEMA),并再进一步和DNA络合后发现:修饰后的PDMAEMA,相应的内涵体逃逸效率得到显著提高;甚至和分子量为2,5000的超支化PEI相比,修饰之后的PDMAEMA的内涵体逃逸能力也更出色,转染效率更高。
In this report, novel endosomal-escape polymers were designed and synthesized from monomers by integrating alkyl and imidazolyl via Passerini reaction and reversible addition-fragmentation chain transfer polymerization(RAFT). After introducing the endosomal-escape polymers with proper degrees of polymerization(DPs) into poly(2-dimethylaminoethyl methacrylate)(PDMAEMA) as the gene delivery vectors, the block copolymers exhibited significantly enhanced hemolytic activity at endosomal p H, and the plasmid DNA(p DNA)-loaded polyplexes showed efficient endosomal escape compared with PDMAEMA, ultimately achieving dramatically increased gene transfection efficacy. These results suggest that the polymers that integrate alkyl and imidazolyl moieties for efficient endosomal escape have wide potential applications for intracellular gene delivery.
In this report, novel endosomal-escape polymers were designed and synthesized from monomers by integrating alkyl and imidazolyl via Passerini reaction and reversible addition-fragmentation chain transfer polymerization(RAFT). After introducing the endosomal-escape polymers with proper degrees of polymerization(DPs) into poly(2-dimethylaminoethyl methacrylate)(PDMAEMA) as the gene delivery vectors, the block copolymers exhibited significantly enhanced hemolytic activity at endosomal p H, and the plasmid DNA(p DNA)-loaded polyplexes showed efficient endosomal escape compared with PDMAEMA, ultimately achieving dramatically increased gene transfection efficacy. These results suggest that the polymers that integrate alkyl and imidazolyl moieties for efficient endosomal escape have wide potential applications for intracellular gene delivery.
引文
[1]Zha,Z.;Li,J.;Ge,Z.ACS Macro Letters.2015,4(10):1123.