Development of a nontoxic and efficient gene delivery vector based on histidine grafted chitosan

To achieve biocompatibility and high gene transfection efficiency, developing new cationic polymers with natural functional moieties has been regarded as a promising way. In this work, histidine was grafted on chitosan (CS) to produce CS derivatives (HGCS) for siRNA delivery and the HGCS/siRNA complexes were formed by the self-assembly method. The structures of histidine grafted CS polymers were characterized by FT-IR and XRD. The Acid-base titration assay was used to measure their proton buffering capacities and results indicated HGCS polymers have stronger buffering capacity than unmodified CS. The particle size, zeta potential and the stability of the polymer/siRNA complexes were measured by laser particle size analyzer and gel retardation assay. The cytotoxicity of polymers was determined by MTT assays in RSC96 cells. Moreover, cellular uptake investigation into polymer/siRNA complexes demonstrated that HGCS polymers have efficient siRNA transfection ability in B16F1 cells and HeLa cells. These data suggest HGCS polymers as a hopeful non-viral gene delivery vectors.