Chitosan nanoparticles in oral squamous cell carcinoma: Formulation strategies, mechanisms, and therapeutic...

According to GLOBOCAN 2022 estimates published by the International Agency for Research on Cancer (IARC), lip and oral cavity cancers accounted for approximately 389,846 new cases and 188,438 deaths worldwide in 2022. Oral squamous cell carcinoma (OSCC) represents the predominant histological subtype of these malignancies. Despite advances in surgery, radiotherapy, and chemotherapy, late diagnosis, systemic toxicity, therapeutic resistance, and poor patient compliance continue to limit clinical outcomes. Nanotechnology-based drug delivery systems have emerged as promising strategies to overcome these challenges, particularly for localized oral cancer therapy. Among various nanocarriers, chitosan nanoparticles have gained significant attention because their mucoadhesive and pH-responsive characteristics improve local retention within the oral cavity, enhance penetration into OSCC tissues, and enable sustained drug release in the acidic tumor microenvironment. This review comprehensively discusses the role of chitosan nanoparticles in OSCC management, highlighting their formulation strategies, including ionic gelation, nanoprecipitation, and green synthesis approaches. Mechanistic insights into cellular uptake, apoptosis induction, reactive oxygen species generation, and gene modulation are critically examined. The therapeutic applications of drug-loaded, phytochemical-loaded, gene-based, and photo-responsive chitosan nanoparticle systems are also summarized. Furthermore, current challenges related to scalability, stability, regulatory approval, and clinical translation are addressed. Overall, chitosan nanoparticles represent a versatile and promising platform for precision and localized therapy in OSCC, with strong potential for future clinical integration.