CAGW peptide modified biodegradable cationic copolymer for effective gene delivery

Abstract

In recent years, gene therapy has become a promising technology to enhance endothelialization of artificial vascular grafts. The ideal gene therapy requires a gene carrier with low cytotoxicity and high transfection efficiency. In this paper, we prepared a biodegradable cationic copolymer poly(D, L-lactide-co-glycolide)-graft-PEI (PLGA-g-PEI), grafted Cys-Ala-Gly-Trp (CAGW) peptide onto this copolymer via the thiol-ene Click-reaction, and then prepared micelles by a self-assembly method. pEGFP-ZNF580 plasmids (pDNA) were condensed by these micelles via electrostatic interaction to form gene complexes. The CAGW peptide enables these gene complexes with special recognition for endothelial cells, which could enhance their transfection. As a gene carrier system, the PLGA-g-PEI-g-CAGW/pDNA gene complexes were evaluated and the results showed that they had suitable diameter and zeta potential for cellular uptake, and exhibited low cytotoxicity and high transfection efficiency for EA.hy926 cells.