• Plant-derived extracellular vesicles (PDEVs) are biocompatible nanocarriers with potential in food science, therapeutics, and regenerative medicine. • This review discusses PDEVs’ isolation, composition, engineering, and roles in immune regulation and tissue repair. • PDEVs show promise in treating inflammatory, hepatic, cardiac, and intestinal injuries, and can be engineered for drug delivery. • Key challenges include isolation standardization, cargo variability, and safety in human applications. Plant-derived extracellular vesicles (PDEVs) are emerging as a new class of natural nanocarriers with significant potential for therapeutic and functional food applications. These biocompatible, orally deliverable vesicles, derived from edible plants, offer several advantages over synthetic and mammalian-derived vesicles, including scalability, safety, and stability in the gastrointestinal environment. Following oral administration, PDEVs can interact with intestinal epithelial cells, immune cells, and gut microbiota, modulating local immune responses, enhancing barrier function, and promoting tissue repair. PDEVs have shown therapeutic efficacy in preclinical models of inflammatory bowel disease, liver injury, myocardial damage, and pulmonary inflammation. Across these models, PDEVs exert common mechanisms of action, including anti-inflammatory effects, antioxidant activity, and cellular regeneration. This review provides an overview of the origins, composition, isolation, and engineering of PDEVs, with a focus on their role as functional nanocarriers for oral delivery. We further discuss the therapeutic potential of PDEVs in tissue regeneration, oxidative stress modulation, and immune regulation across multiple organ systems. Key challenges, including the lack of standardized isolation protocols, cargo heterogeneity, incomplete understanding of biodistribution, and limited long-term safety data, need to be addressed for the successful clinical and commercial translation of PDEVs. The review highlights the need for further research to overcome these barriers and optimize PDEVs for use in both therapeutic and nutraceutical applications.
Chen et al. (Wed,) studied this question.