Efficacy of Chitosan-N-Arginine\nChitosomes in mRNA\nDelivery and Cell Viability Enhancement

Cationic lipid-based carriers are recognized for their\nability\nto complex with mRNA and effectively deliver the mRNA for vaccination\nand therapeutic purposes. However, the significant cytotoxicity of\nthese carriers often restricts their practical application. In the\npresent study, polymer–lipid hybrid nanoparticles, termed chitosomes,\nincorporating chitosan-N-arginine (CSA) with the DOTAP cationic lipid\nand the DOPE helper lipid, were synthesized and evaluated. The addition\nof CSA to the lipid formulations improved their physicochemical stability\nand enhanced mRNA complexation, resulting in high transfection rates\nin the HeLa and HEK293T cell lines. However, the transfection efficiency\nwas low in the NIH-3T3 cell line, indicating a cell type-specific\nresponse to chitosomes. Importantly, CSA significantly reduced the\ncytotoxicity typically associated with DOTAP. Overall, the present\nstudy indicated that optimizing the ratio of CSA to DOTAP is crucial\nfor developing mRNA nanocarriers to achieve high transfection efficiency\nand reduce cytotoxicity across different cell lines.