Peptide modified polycations with pH triggered lytic activity for efficient gene delivery. (6th October 2020)

• Record Type: Journal Article
• Authors: Chen, Xiaojing; Xu, Kai; Yu, Jing; Zhao, Xiaodan; Zhang, Qiang; Zhang, Yanfeng; Cheng, Yilong
• Is Part Of: Biomaterials science. Volume 8:Number 22(2020)
• Page Start: 6301
• Page End: 6308
• Publication Date: 2020-10-06
• Subjects: Biomedical materials -- Periodicals; 610.28
• DOI: 10.1039/d0bm01231a
• Languages: English
• ISSNs: 2047-4830

Abstract

Abstract : C6M3 peptide modified polycations can mediate efficient gene delivery through pH triggered lytic activity for endo/lysosomal escape. Abstract : Endo/lysosome entrapment is the key barrier for gene delivery using synthetic polycations. Although the introduction of a membrane-lytic peptide into polycations could facilitate efficient endo/lysosome release and improve gene delivery efficiency, it is always accompanied by serious safety concerns. In this work, the widely used polycations, poly(2-dimethylaminoethyl methacrylate (PDMAEMA), poly(l -lysine) (PLL) and polyethylenimine (PEI), are modified with a pH-sensitive peptide (C6M3) with selective lytic activity to produce three functional polycations to address the issue of endo/lysosome entrapment and facilitate efficient gene transfer. Hemolysis study shows that the functionalized polycations show good biocompatibility toward red blood cells at neutral pH, and exhibit potent membrane lysis activity under acidic conditions, which are both on-demand for the ideal gene carriers. In vitro transfection studies demonstrate that the peptide modified polycations mediate promising gene delivery efficiency with the luciferase plasmid and the green fluorescence protein plasmid in HeLa cells compared to the parent polycations. Owing to the facile preparation and selective lysis activity of the C6M3 modified polycations, these smart gene vectors may be good candidates for the transfer of various nucleic acids and further clinical gene therapy.