CAGW Peptide Modified Biodegradable Cationic Copolymer for Effective Gene Delivery.

Xinghong Duo,Qian Li,Zaidi Ali,Jun Wang,Yakai Feng,Changcan Shi,Agnaldo Neve,Abdelilah Nejjari,Mary Akpanyung,Wencheng Zhang

doi:10.3390/polym9050158

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.

Highlights

Coronary bypass surgery is one of the most important therapeutic methods for atherosclerotic vascular diseases [1,2]
The cationic copolymer PLGA-g-PEI was synthesized in three steps
The growth of ECs on the surface of artificial blood vessels and the formation of endodermis through rapid endothelialization are beneficial for the promotion of hemocompatibility and the avoidance of restenosis and thrombosis

Summary

Introduction

Coronary bypass surgery is one of the most important therapeutic methods for atherosclerotic vascular diseases [1,2]. The failure of artificial blood vessels after implantation cannot be avoided because of the formation of thrombus caused by their low hemocompatibility. Many strategies have been explored to improve the hemocompatibility and rapid endothelialization of artificial blood vessels [3]. Hydrophilic modification has been proven to be an effective method [4,5]. Lendlein et al grafted different molecular weight and different terminal groups of poly(ethylene glycol) onto the surface of poly(ether amide) material [6]. This surface modification could reduce the adsorption of bovine serum albumin, but the adsorption effect of fibrinogen was not changed

Methods

Results

Conclusion