Biogenesis, preparation, characterization, therapeutic mechanisms and safety evaluation of plant-derived exosome-like nanovesicles in the treatment of ulcerative colitis

Abstract Ulcerative colitis remains a challenging clinical condition due to its complex etiology and the limitations of current therapies. Plant-derived exosome-like nanovesicles (PDELNs) represent a new class of natural nanotherapeutics with significant potential for ulcerative colitis treatment. These nanoparticles exhibit high biocompatibility, the ability to cross biological barriers, and carry a rich cargo of bioactive molecules. This review synthesizes progress in PDELN research over the past decade, focusing on established preparation methods and their multi-targeted therapeutic mechanisms. The current isolation methods of the anti-colitis PDELNs are mainly various types of centrifugation, including ultracentrifugation, differential centrifugation, density gradient centrifugation and their combination. Therapeutically, PDELNs alleviate colitis through potent anti-inflammatory effects, gut microbiota remodeling, and immune response regulation. These effects are attributed to key bioactive components such as plant microRNAs, metabolites, and lipids. Notably, PDELNs demonstrate an excellent safety profile without reported toxicity. Their natural origin, multi-targeted mechanisms, and favorable biosafety profile make PDELNs a promising next-generation therapeutic candidate against colitis, effectively bridging traditional phytotherapy and modern nanomedicine. Graphical Abstract