Chitosan-based nanosystems for cancer diagnosis and therapy: Stimuli-responsive, immune response, and clinical studies

Cancer, a global health challenge of utmost severity, necessitates innovative approaches beyond conventional treatments (e.g., surgery, chemotherapy, and radiation therapy). Unfortunately, these approaches frequently fail to achieve comprehensive cancer control, characterized by inefficacy, non-specific drug distribution, and the emergence of adverse side effects. Nanoscale systems based on natural polymers like chitosan have garnered significant attention as promising platforms for cancer diagnosis and therapy owing to chitosan's inherent biocompatibility, biodegradability, nontoxicity, and ease of functionalization. Herein, recent advancements pertaining to the applications of chitosan nanoparticles in cancer imaging and drug/gene delivery are deliberated. The readers are introduced to conventional non-stimuli-responsive and stimuli-responsive chitosan-based nanoplatforms. External triggers like light, heat, and ultrasound and internal stimuli such as pH and redox gradients are highlighted. The utilization of chitosan nanomaterials as contrast agents or scaffolds for multimodal imaging techniques e.g., magnetic resonance, fluorescence, and nuclear imaging is represented. Key applications in targeted chemotherapy, combination therapy, photothermal therapy, and nucleic acid delivery using chitosan nanoformulations are explored for cancer treatment. The immunomodulatory effects of chitosan and its role in impacting the tumor microenvironment are analyzed. Finally, challenges, prospects, and future outlooks regarding the use of chitosan-based nanosystems are discussed.