Plant-derived extracellular vesicles as natural nanobiotechnology platforms for therapeutic delivery and biomedical applications

Plant-derived extracellular vesicles (PDEVs) are nanoscale vesicles released by plant cells. PDEVs contain heterogeneous combinations of lipids, proteins, nucleic acids, and plant-derived metabolites, enabling interactions with mammalian cells, microorganisms, and other biological systems. Recent advances have expanded understanding of their biogenesis, molecular composition, isolation, characterization, and functional diversity, while also revealing considerable variation among plant sources and vesicle preparations. This review critically summarizes current knowledge of PDEV biology and preparation, including emerging evidence for distinct vesicle populations and advances in purification and physicochemical characterization. We further examine engineering strategies such as cargo loading, surface functionalization, membrane hybridization, and reconstruction using PDEV-derived lipids. Particular emphasis is placed on their reported pharmacological activities in inflammation, cancer, tissue regeneration, and other disease-related models, together with their application as carriers for small molecules, proteins, and nucleic acids. Emerging patent activity and registered clinical studies further illustrate growing translational interest in PDEV-based technologies. However, major challenges remain, including inconsistent nomenclature, lack of standardized isolation and quality-control procedures, cargo heterogeneity, incomplete mechanistic understanding, limited pharmacokinetic and biodistribution data, dose optimization, long-term safety, batch reproducibility, and large-scale manufacturing. Addressing these limitations through standardized, mechanism-driven, and translational research will be essential for advancing PDEVs from experimental bioactive vesicles toward reliable nanobiotechnology platforms for therapeutic delivery and biomedical applications.