Zha Zengshi, Li Junjie, Ge Zhishen
CAS Key Laboratory of Soft Matter Chemistry, Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei 230026, Anhui China.
ACS Macro Lett. 2015 Oct 20;4(10):1123-1127. doi: 10.1021/acsmacrolett.5b00615. Epub 2015 Sep 21.
As one of the toughest tasks in the course of intracellular therapeutics delivery, endosomal escape must be effectively achieved, particularly for intracellular gene transport. 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 pH, and the plasmid DNA (pDNA)-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.
作为细胞内治疗药物递送过程中最艰巨的任务之一，必须有效实现内体逃逸，特别是对于细胞内基因转运而言。在本报告中，通过帕瑟里尼反应和可逆加成-断裂链转移聚合（RAFT）将烷基和咪唑基整合，从单体设计并合成了新型内体逃逸聚合物。将具有适当聚合度（DPs）的内体逃逸聚合物引入聚（甲基丙烯酸2-二甲基氨基乙酯）（PDMAEMA）作为基因递送载体后，嵌段共聚物在内体pH值下表现出显著增强的溶血活性，并且与PDMAEMA相比，负载质粒DNA（pDNA）的多聚体显示出有效的内体逃逸，最终实现了基因转染效率的显著提高。这些结果表明，整合烷基和咪唑基部分以实现有效内体逃逸的聚合物在细胞内基因递送方面具有广泛的潜在应用。
