Exosome-Based Drug Delivery Systems in Colorectal Cancer: Current Evidence and Future Perspectives.

Colorectal cancer (CRC) is one of the most common malignant neoplasms worldwide, being the third most frequently diagnosed cancer and the second leading cause of death. Due to the high incidence of CRC cases, its biological complexity, and high morbidity and mortality, the development of more effective and less aggressive therapeutic approaches is an urgent need. Extracellular vesicles (EVs), especially EXs, are a very viable alternative as a nanocarrier for anticancer molecules for the treatment of CRC, as EXs are biologically relevant EVs with considerable therapeutic potential. EXs are nanoscale vesicles approximately 30-200 nm in diameter, identical in composition to the membrane of their parent cells, and carry a bioactive cargo of proteins, lipids, nucleic acids, and glycoconjugates. Beyond their physiological functions, EXs are gaining prominence as next-generation drug delivery platforms. Their ability to improve the efficacy of antitumor therapies, potentially reducing adverse effects associated with conventional chemotherapy and radiotherapy, makes them very promising. Furthermore, functionalizing the surface with targeting ligands, such as MUC1 aptamers, AS1411, or iRGD peptides, can further increase its specificity for CRC cells. Advances in drug delivery techniques, including passive incubation, electroporation, and chemical modification, have enabled the incorporation of conventional chemotherapeutic agents such as doxorubicin, 5-fluorouracil, and SN-38, as well as nucleic acid-based therapies, including microRNA and siRNA. Due to the limitations and invasive nature of current treatments for CRC, new studies to obtain innovative and targeted therapeutic strategies are essential to reduce harmful effects. Therefore, exosome-based drug delivery systems represent a promising and clinically relevant avenue for future cancer therapy.