A Facile Strategy to Prepare Hyperbranched Hydroxyl-Rich Polycations for Effective Gene Therapy
A Facile Strategy to Prepare Hyperbranched Hydroxyl-Rich Polycations for Effective Gene Therapy
复制标题
制备用于有效基因治疗的超支化富含羟基聚阳离子的简便策略
DOI：
10.1021/acsami.6b11029
复制
发表时间：
2016-11-02
影响因子：
9.5
通讯作者：
Xu, Fu-Jian
中科院分区：
文献类型：
--
作者：
Duan, Shun;Yu, Bingran;Xu, Fu-Jian
因此，低毒性、高转染效率的非病毒基因载体是基因治疗的重要手段。在这项工作中，我们开发了一个简单的策略，通过一锅法，包括两个常用的试剂之间的开环反应，乙二胺（艾德）与两个氨基和1，3，5-三缩水甘油基异氰脲酸酯（TGIC）与三个环氧基团的开环反应，制备超支化的富羟基聚阳离子（表示为TE）。研究了不同分子量的超支化TEs的DNA缩合能力、蛋白质吸附性能、生物相容性、转染效率以及体内肿瘤治疗和毒性。由于TE含有丰富的羟基，因此具有较低的细胞毒性和蛋白质吸收性能。TE的最佳转染效率显著高于金标准聚阳离子基因载体支链聚乙烯亚胺（PEI，25 kDa）。此外，TE通过递送抗癌基因p53而被应用于体内肿瘤抑制，其显示出良好的抗肿瘤效率且副作用低。本工作为制备具有良好转染性能的超支化富羟基聚阳离子载体提供了新的思路。
For effective gene therapy, nonviral gene carriers with low toxicity and high transfection efficiency are of much importance. In this work, we developed a facile strategy to prepare hyperbranched hydroxyl-rich polycations (denoted by TE) by the one-pot method involving ring-opening reactions between two commonly used reagents, ethylenediamine (ED) with two amino groups and 1,3,5-triglycidyl isocyanurate (TGIC) with three epoxy groups. The hyperbranched TEs with different molecular weights were investigated on their DNA condensation ability, protein absorption property, biocompatibility, transfection efficiency, and in vivo cancer therapy and toxicity. TE exhibited low cytotoxicity and protein absorption property due to the plentiful hydroxyl groups. The optimal transfection efficiency of TE was significantly higher than that of the gold standard polycationic gene carrier branched polyethylenimine (PEI, 25 kDa). Furthermore, TE was applied for in vivo tumor inhibition by the delivery of antioncogene p53, which showed good antitumor efficiency with low adverse effects. The present work provides a new concept for the facile preparation of hyperbranched hydroxyl-rich polycationic carriers with good transfection performances.