A novel, non-toxic chitosan modified with lysine to enhance buffer capacity for siRNA delivery

The present study employed lysine as a modifying agent for chitosan (CS) to synthesise a novel CS derivative (LGCS) intended for siRNA delivery. The successful grafting of lysine to CS was characterized using FT-IR and the introduction of the lysine moiety resulted in improved solubility and buffering capacity of CS. The Zeta potential and size of LGCS/siRNA nanoparticles (NPs) were evaluated using dynamic light scattering (DLS) and the results were verified by transmission electron microscopy (TEM). Evaluation of LGCS's siRNA binding capacity was conducted using a gel retardation assay. The results showed that LGCS could effectively bind to siRNA and form a complex with a hydrated diameter of about 97.2 ± 1.3 nm. Furthermore, cytotoxicity assays conducted on RSC96 cells demonstrated that LGCS exhibited lower toxicity compared to linear polyethyleneimine (PEI) 25k. In vitro, cellular uptake assays also revealed that LGCS displayed excellent transfection efficiency. The results of our study lead us to the conclusion that LGCS holds great promise as a gene delivery vector.