Chitosan nanovectors for siRNA delivery: New horizons for nonviral gene therapy

The growing interest in RNA-based therapeutics has positioned small interfering RNA (siRNA) as a promising tool for gene silencing with high specificity and efficacy. However, the successful clinical application of siRNA therapies requires efficient delivery systems to overcome extracellular and intracellular barriers. Chitosan, a naturally derived polysaccharide, has gained significant attention as a non-viral vector due to its biodegradability, biocompatibility, mucoadhesive properties, and capacity to enhance cellular uptake. These attributes make chitosan an attractive alternative to lipid-based nanoparticles, which currently dominate siRNA delivery platforms. Recent advancements in chitosan-based nanoformulations, including chemical modifications and functionalization strategies, have improved siRNA stability, targeting efficiency, and transfection potential, addressing key limitations such as low bioavailability and immunogenicity. Despite these advances, challenges remain in achieving optimal release kinetics, scalability, and consistent therapeutic efficacy. Future research efforts will focus on engineering chitosan derivatives with enhanced physicochemical properties, integrating multifunctional nanocarriers, and refining formulation strategies to bridge the gap between preclinical research and clinical translation. The continued development of chitosan-based siRNA therapeutics holds significant potential for advancing precision medicine and expanding treatment options for a variety of diseases, including cancer, metabolic disorders, and inflammatory conditions.