State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences , Beijing 100021, China.
ACS Appl Mater Interfaces. 2016 Nov 2;8(43):29334-29342. doi: 10.1021/acsami.6b11029. Epub 2016 Oct 18.
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.
为了实现有效的基因治疗，低毒性和高转染效率的非病毒基因载体非常重要。在这项工作中，我们开发了一种简便的策略，通过一锅法制备超支化羟基丰富的聚阳离子（表示为 TE），该方法涉及两种常用试剂之间的开环反应，这两种试剂分别是具有两个氨基的乙二胺（ED）和具有三个环氧基团的 1,3,5-三缩水甘油异氰尿酸酯（TGIC）。研究了不同分子量的超支化 TE 在 DNA 凝聚能力、蛋白质吸附性能、生物相容性、转染效率、体内癌症治疗和毒性方面的性能。由于大量的羟基，TE 表现出低细胞毒性和蛋白质吸附性能。TE 的最佳转染效率明显高于金标准阳离子基因载体支化聚乙烯亚胺（PEI，25 kDa）。此外，通过递送抑癌基因 p53，TE 被用于体内肿瘤抑制，其表现出良好的抗肿瘤效果，副作用低。本工作为制备具有良好转染性能的超支化羟基丰富的阳离子载体提供了一个新概念。
