Exosome-based mucosal therapeutic and diagnostic system: towards clinical translation

The mucosa, as the body's largest immune organ, is involved in various diseases such as ulcerative colitis, respiratory conditions, and tumors. Mucosal delivery offers favorable patient compliance, strong localized therapeutic effects, and the ability to treat a broad spectrum of diseases. However, the multilayered barrier structure of mucosal tissues often hinders effective drug delivery. Although current nanotechnologies have demonstrated some success in overcoming mucosal barriers, they still encounter challenges such as immunogenicity, low stability, high production costs, and difficulties in clinical translation. Extracellular vesicles (EVs), natural nanoscale lipid bilayer vesicles found in plants, animals, microorganisms, and body fluids, possess high biocompatibility, low immunogenicity, targeted delivery, and an excellent capacity to cross biological barriers. Exosomes, a subtype of EVs, are emerging as promising bio-nanotherapeutic tools capable of addressing limitations that conventional nanoparticles cannot. Their cargo of nucleic acids and proteins enables both therapeutic and diagnostic functions across various diseases. Exosomes can effectively traverse mucosal barriers-including gastrointestinal, nasal, and ocular mucosa-thereby offering a potential solution to mucosal delivery challenge. Moreover, exosomes derived from mucosal secretions may serve as biomarkers for diagnosing mucosa-associated diseases, providing a non-invasive and easily accessible alternative to blood samples. This review aims to elucidate the therapeutic roles and mechanisms of exosomes from different sources as drug carriers or therapeutic agents in diseases treated via transmucosal delivery. It also summarizes the diagnostic potential of mucosal secretion-associated exosomes. In conclusion, this paper underscores the importance of exosomes in mucosal delivery, discusses their current limitations and future promise, and provides new insights into their clinical applications.