Study on the transfection efficiency of chitosan‐based gene vectors modified with poly‐l‐arginine peptides

Abstract

Although in a series of studies, arginine peptides had shown the ability to promote the targeting delivery efficacy, the relationship between the transfection efficiency and the length of the poly-l-arginine chain had seldom been reported. This study was aimed to explore whether the chain length of poly-l-arginine grafted on chitosan had a great significance on the transfection efficiency of entering the cells. Herein, arginine and arginine peptide modified chitosan were synthesized as gene vectors (CS-Arg and CS-5Arg) and then the chemical structures were characterized by using 1 H NMR. The CS-Arg and CS-5Arg were combined with plasmids by electrostatic interactions to form stable particles. The morphology features, Zeta potentials, and buffering capacity of the complex particles were analyzed. Afterward, the combination ability with DNA and the protection ability to DNase I were studied, and the gene transfection efficiency and cellular uptake were investigated in vitro. The results showed that the gene transfection efficiency of the chitosan was significantly enhanced by arginine-graft modification. However, there were no significant differences between the CS-Arg and the CS-5Arg. The molecular simulation results indicated that the guanidine groups of grafted arginine were shielded by chitosan molecule and the guanidine groups contributed little to the gene transfection efficiency. The results demonstrated that the increased chain length of grafted arginine had no significantly enhanced effect on the transfection efficiency, which could provide convincing evidence for the construction and application of arginine and chitosan derivatives as gene vectors, and could promote the development of gene delivery system.

A Ternary Synergistic eNOS Gene Delivery System Based on Calcium Ion and L-Arginine for Accelerating Angiogenesis by Maximizing NO Production

“…The results demonstrated that the gene transfection efficiency of chitosan was significantly enhanced after arginine-graft. 30 Based on its positive charge and guanidine structure under physiological conditions, arginine is widely used as a drug and gene carrier. 31 To confirm the synergistic role of the ternary gene delivery system in bioactive NO production, we assessed the amount of NO released after different treatments and its impact on ECs including angiogenesis-related functions and antiinflammatory functions.…”

Plasma Modification Techniques for Natural Polymer-Based Drug Delivery Systems

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A cationic lipid with advanced membrane fusion performance for pDNA and mRNA delivery

“…Inspired by the cellpenetrating peptides (CPP) in viruses, several arginine-rich residues have been introduced into the hydrophilic segment of lipidic carriers. For instance, linear, 8 dendritic, 9 and clustered 10 This journal is © The Royal Society of Chemistry 2023 arginine all showed an enhanced transfection efficiency compared with controls. The guanidine of arginine could form bidentate hydrogen bonds with the negative phosphates, sulfates, and carboxylates on the cell surface and be driven into cells.…”