Plant-Derived Nanovesicles: From Biogenesis and Lipid Fingerprints to Gut-Organ Axis and Smart Biomaterial Platforms

Plant-derived nanovesicles (PDNVs) are natural bioactive nanocarriers, yet existing reviews remain fragmented across immunology, drug delivery, and engineering. This review provides the first integrated framework bridging plant cell biology, immunology, materials science, and nanomedicine to present a complete biogenesis-composition-immunomodulation-engineering-translation continuum for PDNVs. We systematically compare three biogenesis pathways-multivesicular body (MVB), plasma membrane budding, and the plant-specific exocyst-positive organelle (EXPO) pathway-and delineate the unique lipid fingerprints of each vesicle subpopulation. We profile four functional cargo classes-lipids, proteins, RNAs, and secondary metabolites-emphasizing their synergistic bioactivities. Uniquely, we synthesize the emerging paradigm of systemic remote organ regulation through the gut-brain, gut-liver, and gut-kidney axes within a single framework. We provide a systematic overview of PDNV integration with smart biomaterials, including ROS-responsive hydrogels, metal-organic frameworks (MOFs), and tripartite hydrogel-MOF-PDNV platforms. Finally, we critically analyze translational bottlenecks-standardization, mechanistic depth, and regulatory pathways, and systematically subdivide translational bottlenecks into four core industrial challenges: ambiguous underlying molecular mechanisms, the absence of unified standardized preparation pipelines, inherent limitations of vesicle material engineering, and incomplete clinical supervision and regulatory frameworks; corresponding targeted strategies are further proposed to resolve these barriers and accelerate clinical adoption. By bridging disciplines and filling critical literature gaps, this review offers a unified framework to guide both fundamental research and clinical translation of PDNVs as next-generation precision nanomedicines.