Chitosan and Its Derivative-Based Nanoparticles in Gastrointestinal Cancers: Molecular Mechanisms of Action and Promising Anticancer Strategies

Gastrointestinal cancers account for a significant health concern as the existing treatment modalities, such as surgery, chemotherapy, and radiation therapy, exhibit considerable drawbacks, including a high probability of recurrence, insufficient drug specificity, and severe adverse effects. Hence, novel therapeutic approaches and enhanced tissue-specific targeting are required. Nanomedicine is a field of medicine that uses nanoscale carriers for targeting and administering drugs or diagnostic agents to particular tissues. In the field of nanomedicine, chitosan nanoparticles are well-established delivery technologies used as polymeric carriers. Chitosan is a natural carbohydrate that is biocompatible, biodegradable, polycationic, and mucoadhesive. Chitosan has shown promise in the administration of chemotherapeutic drugs, gene therapy, and immunotherapy for the treatment of gastrointestinal cancers. The limited water solubility of chitosan is one of its major disadvantages as a drug delivery system. Thus, solubility may be increased by chemically treating chitosan. Chitosan derivatives improve the activity, selectivity, biocompatibility, and therapeutic dose reduction of anticancer drugs when used in hydrogel, emulsion, surfactant formulations, and nanoformulation. Chitosan and its derivatives have shown effectiveness in nanoparticle production and exhibit unique surface properties, enabling them to interact selectively with gastrointestinal tumors through both active and passive targeting mechanisms. This review focuses on the molecular signaling pathways of chitosan nanoparticles and their derivatives as potential anticancer agents. The potential of future chitosan applications in gastrointestinal cancers is additionally highlighted.