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新型星形载体由β-环糊精核心和二硫键连接的聚(甲基丙烯酸缩水甘油酯)衍生物臂组成,具有丰富的侧链仲胺和羟基,可实现高效的基因传递。

New star-shaped carriers composed of β-cyclodextrin cores and disulfide-linked poly(glycidyl methacrylate) derivative arms with plentiful flanking secondary amine and hydroxyl groups for highly efficient gene delivery.

机构信息

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

出版信息

ACS Appl Mater Interfaces. 2013 Feb;5(3):703-12. doi: 10.1021/am302249x. Epub 2013 Jan 14.

Abstract

The biocleavable star-shaped vectors (CD-SS-PGEAs) consisting of nonionic β-cyclodextrin (β-CD) cores and disulfide-linked low-molecular-weight poly(glycidyl methacrylate) (PGMA) derivative arms with plentiful flanking secondary amine and hydroxyl groups were successfully proposed for highly efficient gene delivery. A simple two-step method was first adopted to introduce reduction-sensitive disulfide-linked initiation sites of atom transfer radical polymerization (ATRP) onto β-CD cores. The disulfide-linked PGMA arms prepared subsequently via ATRP were functionalized via the ring-opening reaction with ethanolamine (EA) to produce the cationic EA-functionalized PGMA (PGEA) arms with plentiful secondary amine and nonionic hydroxyl units. The cationic PGEA arms can be readily cleavable from the β-CD cores under reducible conditions. Such biocleavable star-shaped CD-SS-PGEA vectors possessed the good pDNA condensation ability, low cytotoxicity, and efficient gene delivery ability.

摘要

由非离子β-环糊精(β-CD)核和通过巯基连接的低分子量聚(甲基丙烯酸缩水甘油酯)(PGMA)衍生臂组成的生物可裂解星形载体(CD-SS-PGEAs),具有丰富的侧基仲胺和羟基,被成功地提出用于高效基因传递。首先采用简单的两步法将还原敏感的二硫键连接的原子转移自由基聚合(ATRP)引发点引入β-CD 核中。随后通过 ATRP 制备的二硫键连接的 PGMA 臂通过与乙醇胺(EA)的开环反应进行功能化,生成具有丰富仲胺和非离子羟基单元的阳离子 EA 功能化 PGMA(PGEA)臂。阳离子 PGEA 臂可以在还原条件下从β-CD 核中轻易地断裂。这种生物可裂解的星形 CD-SS-PGEA 载体具有良好的 pDNA 凝聚能力、低细胞毒性和高效的基因传递能力。

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