From crop stress to host response: plant extracellular vesicles as dynamic exposure vectors in food and botanical toxicology.

Plant-derived extracellular vesicles and vesicle-like nanoparticles are increasingly discussed as stable natural carriers in foods, botanical preparations and nanomedicine. That framing overlooks a central toxicological variable: the source plant is a responsive biological system whose cultivar, organ, developmental stage and stress history can alter vesicle release and cargo before harvest. Drought, salinity, temperature, pathogens, wounding, nutrient imbalance and agricultural chemicals may therefore change not only crop composition but also the membrane-bound biological dose presented to oral, intestinal, dermal or respiratory barriers. This Review develops a crop-to-host framework for plant extracellular-vesicle toxicology. It distinguishes apoplastic extracellular vesicles from homogenate-derived vesicle-enriched fractions, traces how cultivation, harvest, processing, storage and digestion reshape identity and exposure, and evaluates mechanisms involving barrier uptake, microbiome interactions, innate immune sensing, lipid and protein cargo, small RNAs, co-isolated phytochemicals and environmental contaminants. Current evidence is strongest for particle isolation, selected cargo transfer and engineered delivery, but remains weak for real-world dietary dose, stress-dependent cargo changes, chronic exposure and adverse outcomes. We propose an evidence ladder and a human-relevant testing strategy combining crop-side metadata, orthogonal vesicle characterization, contaminant mass balance, gastrointestinal digestion, intestinal organoids, gut-liver microphysiological systems, immune modules and quantitative in vitro-in vivo extrapolation. Treating plant physiological history as part of exposure definition could convert plant vesicles from poorly specified "natural nanoparticles" into measurable and testable entities for food, botanical and environmental toxicology.