基于分子胶的嵌段共聚物胶束在药物基因载体中的应用
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- 英文论文题名：Applications of block copolymer micelles as drug/gene delivery carrier
- 论文作者：沈玉梅 ; 龚兵 ; 杨晴来 ; 何昌玉
- 英文论文作者：Yu-Mei Shen ; Bing Gong ; Qinglai Yang ; Changyu He ; Shanghai Center for Systems Biomedicine ; Ministry of Education Key Laboratory of Systems Biomedicine ; Shanghai Jiao Tong University
- 年：2016
- 作者机构：上海交通大学系统生物医学研究院;
- 论文关键词：敏感型共聚物 ; 基因载体 ; 双二硫键
- 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：O631;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：187k
- 原文格式：D
- 会议级别：全国
摘要
嵌段共聚物自组装胶束在药物基因输送中的应用受到了广泛关注,理想的靶向输送体系能安全稳定穿越各种屏障从而把药物输送至靶细胞,并可在细胞内控制释放。我们基于氢键序列选择性作用下双重二硫键(分子胶)的形成,得到了两亲性嵌段共聚物。由于分子胶的作用,极大地抑制了自身偶联产物的形成,而交叉偶联产物成为绝对主产物。反应生成的交叉偶联产物即两亲性嵌段共聚物可以自组装为纳米胶束,并作为药物靶向输送体系,表现出良好的稳定性、低毒性,载药胶束到达肿瘤细胞后在GSH作用下能够将所包裹的疏水药物释放。而胶束表面叶酸的存在,得到一种具有靶向作用的纳米药物载体。应用类似的方法,对于PEI-PLA-PEG三嵌段共聚物胶束,可同时用于mi RNA转染,从而得到更具有发展前景的药物运输载体。聚乙烯亚胺(PEI)在多种细胞和组织中都具有良好的基因转染效果。我们合成的三嵌段共聚物PEI-PLA-PEG自组装胶束。由于较高的转染效率及良好的生物相容性,具有作为药物基因载体的发展前景。
Block copolymer self-assembled micelles have received intensive interest in drug/gene delivery system. Because of the existence of redox potential gradients between extra-and intracellular spaces polymeric micelles with redox-responsiveness possess multiple advantageous features for controlled release. We constructed amphiphilic block copolymers using association units allowing H-bonded instructed, directional but reversible disulfide bond formation which ensures the controlled coupling of cross-linked product, the gene drug would to be triggered by external stimuli GSH. Polyethyleneimine(PEI) is most widely investigated for gene delivery. PEI-based polymers can lead to high transfection efficiency due to so-called "proton sponge effect''. Herein we report a new amphiphilic triblock copolymers PEI-PLA-PEG that rely on sequencing specific association with double disulfide linkages, also consisting of hydrophilic block B(PEG), a hydrophobic block A(PLA) and block C(PEI) as cationic fragments. The amphiphilic triblock copolymers can self-assemble into micelles in aqueous. Ascribed to the perfect biocompatibility, efficient targeting and redox-responsive properties, the self-assembled micells are endowed with a charming opportunity to extend into effective drug/gene delivery systems for therapeutic applications. Key Words: Stimuli-responsive copolymer; gene delivery; double disulfide linkages.
Block copolymer self-assembled micelles have received intensive interest in drug/gene delivery system. Because of the existence of redox potential gradients between extra-and intracellular spaces polymeric micelles with redox-responsiveness possess multiple advantageous features for controlled release. We constructed amphiphilic block copolymers using association units allowing H-bonded instructed, directional but reversible disulfide bond formation which ensures the controlled coupling of cross-linked product, the gene drug would to be triggered by external stimuli GSH. Polyethyleneimine(PEI) is most widely investigated for gene delivery. PEI-based polymers can lead to high transfection efficiency due to so-called "proton sponge effect''. Herein we report a new amphiphilic triblock copolymers PEI-PLA-PEG that rely on sequencing specific association with double disulfide linkages, also consisting of hydrophilic block B(PEG), a hydrophobic block A(PLA) and block C(PEI) as cationic fragments. The amphiphilic triblock copolymers can self-assemble into micelles in aqueous. Ascribed to the perfect biocompatibility, efficient targeting and redox-responsive properties, the self-assembled micells are endowed with a charming opportunity to extend into effective drug/gene delivery systems for therapeutic applications. Key Words: Stimuli-responsive copolymer; gene delivery; double disulfide linkages.
引文
[1]Yang,Q.;Bai,L.;Zhang,Y.;Xu,Y.;Shao,Z.;Shen,Y.;Gong,B.Macromolecules 2014,47:7431-7441.
[2]Yang,Q.;Tan,L.;He,C.;Liu,B.;Xu,Y.;Shao,Z.;Gong,B.;Shen,Y.Acta Biomaterialia 2015,17:193-200.
[3]Yang,Q.;He,C.;Xu,Y.;Liu,B.;Shao,Z.;Zhu,Z.;Gong,B.;Shen,Y.Polymer Chemistry 2015,6:1454-1464.
[4]Yang,Q.;He,C.;Liu,B.;Zhu,Z.;Shao,Z.;Gong,B.;Shen,Y.Polymer 2016,90,351-362.
[2]Yang,Q.;Tan,L.;He,C.;Liu,B.;Xu,Y.;Shao,Z.;Gong,B.;Shen,Y.Acta Biomaterialia 2015,17:193-200.
[3]Yang,Q.;He,C.;Xu,Y.;Liu,B.;Shao,Z.;Zhu,Z.;Gong,B.;Shen,Y.Polymer Chemistry 2015,6:1454-1464.
[4]Yang,Q.;He,C.;Liu,B.;Zhu,Z.;Shao,Z.;Gong,B.;Shen,Y.Polymer 2016,90,351-362.