文献类型：期刊文献

英文题名：Module-combinatorial design and screening of multifunctional polymers based on polyaspartic acid for DNA delivery

作者：Xia, Qianying[1];Jing, Qiufang[1,2];Lu, Chunjie[1];Guo, Xiaoyan[2];Chen, Xinyu[1];Tang, Chenglan[3];Han, Jiaxin[3];Wang, Hongxun[4];Dong, Yanpeng[4];Fang, Pengfei[4];Zhang, Dahe[4];Teng, Xiaonuo[4];Ren, Fuzheng[1,2,3]

机构：[1]East China Univ Sci & Technol, Shanghai Frontiers Sci Ctr Optogenet Tech Cell Met, Sch Pharm, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China;[3]East China Univ Sci & Technol, Engn Res Ctr Pharmaceut Proc Chem, Sch Pharm, Minist Educ, Shanghai 200237, Peoples R China;[4]Suzhou Womei Biol Co Ltd, Suzhou 215613, Peoples R China

年份：2024

卷号：661

外文期刊名：INTERNATIONAL JOURNAL OF PHARMACEUTICS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001287861800001)】；

基金：This work was supported by Shanghai Key Laboratory of New Drug Design (Grant No. 17DZ2271000) , and Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism (Shanghai Municipal Education Commission) .

语种：英文

外文关键词：Polyaspartic acid; Combinatorial design; DNA; Polyplexes; Vaccine

摘要：It is crucial to develop non-viral gene vectors that can efficiently and safely transfect plasmid DNA into cells. Low transfection efficiency and high cytotoxicity of cationic polymers hinder their application as gene carriers. Modification of cationic polymers has emerged as an attractive strategy for efficient and safe nucleic acids delivery. In this study, a simple and rapid method is developed to synthesize a series of multifunctional polymers by utilizing biodegradable polyaspartic acid as the backbone and modifying it with three modules. This onecomponent polymer possesses capabilities for nucleic acid condensation, cellular uptake, and endosomal escape. Polymers containing imidazole, triazole, or pyridine group exhibited promising transfection activity. Substituted with dodecylamine or 2-hexyldecan-1-amine enhance cellular uptake and subsequent transfection. Furthermore, the influence of ionizable amine side chains on gene delivery is investigated. Two optimal polymers, combined with the avian encephalomyelitis virus (AEV) plasmid vaccine, induced robust specific antibody responses and cellular immune responses in mice and chickens. Through module-combination design and screening of polyaspartamide polymers, this study presents a paradigm for the development of gene delivery vectors.