Chitosan-Based polymeric nanocarriers for non-melanoma skin cancer: microchemical design, mechanisms, and translational potential

Non-melanoma skin cancers (NMSCs), primarily basal and squamous cell carcinomas, are among the most frequently diagnosed malignancies worldwide, often resulting from chronic ultraviolet (UV) radiation exposure. Current treatments such as surgical resection, radiotherapy, and systemic chemotherapy are limited by invasiveness, poor selectivity, and undesirable side effects. Chitosan, a naturally derived, biodegradable polysaccharide has gained attention as a nanocarrier due to its intrinsic biocompatibility, mucoadhesiveness, and antitumor properties. However, its native limitations, including poor aqueous solubility and restricted drug loading, have necessitated chemical and structural modifications to enhance its clinical utility. Recent advancements in microchemical synthesis and nanoscale engineering have led to the development of modified chitosan-based delivery systems with improved solubility, targeted drug release, and enhanced interaction with tumor microenvironments. This review provides a comprehensive analysis of chitosan nanocarrier design, drug encapsulation strategies, and mechanistic pathways relevant to NMSC therapy. Emphasis is placed on the physicochemical characterization, cellular uptake, and preclinical outcomes of these systems. Finally, the review discusses translational barriers, including regulatory hurdles, batch reproducibility, and large-scale manufacturing, outlining a path toward the clinical application of chitosan nanomedicine in skin cancer treatment.