应用化学2025，Vol.42Issue(10)：1335-1348,中插1-中插3,17.DOI:10.19894/j.issn.1000-0518.250219
基于超支化聚赖氨酸的mRNA递送载体
Hyperbranched Polylysine-Based mRNA Delivery Carrier Optimization and Evaluation
摘要
Abstract
Hyperbranched polylysine(HPL)is a synthetic polymer material that is simple to prepare and inexpensive,with excellent biocompatibility.However,its transfection efficiency is not good when used as an mRNA delivery carrier.In this study,a HPL material library was established through a simple and systematic chemical modification strategy.Through amino-epoxide ring-opening reactions,Michael addition reactions,and amino-phospholane ring-opening reactions,small molecules containing hydrophobic groups such as 1,2-epoxides,acrylates,and alkylated dioxyphosphoranes were introduced into the three-dimensional backbone of HPL,and mRNA delivery carriers with high transfection efficiency were screened.Experimental results showed that HPL modified with propylene oxide(E3),HPL-E3,was the best material in the HPL-En series,with a 1.8-fold increase compared to unmodified HPL;HPL modified with 3-(perfluorobutyl)-1,2-epoxide(F9),HPL-F9,was the best material in the HPL-Fx series,with a 272.4-fold increase compared to unmodified HPL;HPL modified with dodecyl acrylate(A12),HPL-A12,was the best material in the HPL-Ay series,with a 3246-fold increase compared to unmodified HPL;and HPL modified with 2-octyloxy-2-oxy-1,3,2-dioxaphospholane(P8),HPL-P8,was the best material in the HPL-Pm series,with a 75.0-fold increase compared to unmodified HPL.This minimalist one-step synthesis strategy can introduce hydrophobic chain segments of appropriate lengths to enhance cell uptake,and can also convert primary amines on HPL to secondary or tertiary amines,thereby enhancing their endosomal escape capability,providing a new method for the construction of mRNA delivery carriers.关键词
超支化聚赖氨酸/mRNA递送/环氧化合物/丙烯酸酯/烷基化二氧磷杂环戊烷Key words
Hyperbranched polylysine/mRNA delivery/Epoxy compound/Acrylate ester/Alkylated dioxyphosphorinane分类
化学化工引用本文复制引用
齐翊博,吕坤城,王译伟,宋万通,季生象,陈学思..基于超支化聚赖氨酸的mRNA递送载体[J].应用化学,2025,42(10):1335-1348,中插1-中插3,17.基金项目
科技部重点研究计划项目(Nos.2024YFA1212200,2024YFB3814800)、国家自然科学基金(No.22222509)和吉林省生物医用高分子材料国际合作重点实验室(No.YDZJ202402077CXJD)资助Supported by the National Key Research and Development Program of China(Nos.2024YFA1212200,2024YFB3814800),the National Natural Science Foundation of China(No.22222509)and Jilin Provincial Key Laboratory of Biomedical Polymer Materials for International Cooperation(No.YDZJ202402077CXJD) （Nos.2024YFA1212200,2024YFB3814800）
