Phytochemical-Primed Extracellular Vesicles and Plant-Derived Exosome-Like Nanoparticles as Endogenous Nanomedicine...

The mismatch between the low oral bioavailability of many phytochemicals and their broad systemic efficacy remains a central challenge for natural-product pharmacology and nanomedicine. Rather than relying solely on direct drug-target interactions at distant tissues, accumulating evidence suggests that phytochemicals can act at primary interfaces such as the intestinal epithelium, liver, tumor stroma, and immune microenvironment to alter EV biogenesis or cargo in selected models, while effects on tissue homing remain largely proposed. In this review, we discuss these findings from a vesicle-enabled nanomedicine perspective, highlighting how phytochemical-primed host EVs and plant-derived exosome-like nanoparticles (PELNs) may function as biogenic signal carriers that translate local chemical exposure into systemic therapeutic regulation. We summarize reported links between bioactive compounds and EV release, cargo loading, and membrane remodeling, while distinguishing directly demonstrated mechanisms from proposed ones. We further discuss how surface molecules including integrins and tetraspanins shape organotropism, blood-brain barrier transport, tumor pre-metastatic niche formation, and gut-liver or neuro-vascular communication. Special attention is given to the translational value of EVs and PELNs as natural nanocarriers for poorly soluble phytochemicals, as liquid-biopsy biomarkers of treatment response, and as quality-controllable platforms for traditional Chinese medicine (TCM)-derived interventions. Here, "vesicular information" refers to the measurable molecular cargo and surface features of a vesicle preparation. This emerging model does not yet establish that phytochemical-modified EVs explain the bioavailability paradox in all settings.