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

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.