Highly branched poly(β-amino ester)s with narrow molecular weight distribution: Fractionation and gene transfection activity

作     者：Chenfei Wang Litao Sun Qiuxia Li Zhili Li Chengyuan Xu Xinyue Zhang Jianjun Shi Hao Zhou Wenxin Wang Dezhong Zhou Chenfei Wang;Litao Sun;Qiuxia Li;Zhili Li;Chengyuan Xu;Xinyue Zhang;Jianjun Shi;Hao Zhou;Wenxin Wang;Dezhong Zhou

作者机构：School of Chemical Engineering and TechnologyXi’an Jiaotong UniversityXi’an 710049China Key Laboratory of Water Pollution Treatment&Resource ReuseHainan Normal UniversityHaikou 571158China State Key Laboratory of Medicinal Chemical BiologyTianjin Key Laboratory of Protein Scienceand College of Life SciencesNankai UniversityTianjin 300071China Department of DermatologyThe Second Hospital Affiliated to Xi’an Jiaotong UniversityXi’an 710061China Charles Institute of DermatologySchool of MedicineUniversity College DublinDublin 4Ireland 

出 版 物：《Chinese Chemical Letters》 (中国化学快报（英文版）)

年 卷 期：2023年第34卷第3期

页      面：383-387页

核心收录：

学科分类：0710[理学-生物学] 07[理学] 071007[理学-遗传学] 

基　　金：funded by the National Natural Science Foundation of China(NSFC,No.51903202) Hainan Provincial Natural Science Foundation of China(No.521RC1058) the Key R&D Program of Shaanxi Province(No.2020GXLH-Y-016) the Natural Science Foundation of Shaanxi Province(No.2020JM-055) the Fundamental Research Funds for the Central Universities(No.xtr042019020) the Young Talents Support Plan of Xi’an Jiaotong University(No.HG6J002) 

主　　题：Gene transfection Non-viral vector Highly branched poly(β-amino ester)s Fractionation Transfection activity 

摘      要：Highly branched poly(β-amino ester)s(HPAEs) have shown their great promise in gene delivery. However, their broad molecular weight distribution(MWD) poses an additional challenge to the mechanistic understanding of the influence of molecular weight(MW) on their gene transfection activity. Using a stepwise precipitation strategy, HPAEs were fractionated. It is shown that MW has a significant effect on the transfection activity and cytotoxicity of HPAEs. The intermediate MW mediates higher transfection efficiency while maintaining high cell viability. Mechanistic studies show that the intermediate MW confers stronger DNA binding affinity to HPAEs, leading to the formulation of polyplexes with a relatively smaller size and more positive zeta potential. This study not only suggests a simple strategy to fractionate HPAEs with narrow MWD but also provides new insights into understanding the structure-property relationship, which would facilitate the clinical translation of HPAEs in gene therapy.