MicroRNAs in Edible Plant-Derived Extracellular Vesicles: Stability, Oral Delivery, and Cross-Kingdom Biological Effects

Edible plant-derived extracellular vesicles (EVs) and EV-like nanoparticles have attracted interest as potential carriers of microRNAs (miRNAs) across the gastrointestinal tract. This critical narrative review examines their terminology, isolation and characterization, RNA composition, gastrointestinal stability, cellular uptake, biodistribution, biological effects, and potential applications. Available studies indicate that plant-derived particle preparations can associate with diverse RNAs and interact locally with intestinal epithelial cells, immune cells, stem/progenitor cells, and gut microorganisms. However, particles recovered from homogenized tissues or juices may include intracellular vesicles, membrane fragments, and non-vesicular complexes; detection of miRNAs in particle-enriched fractions therefore does not establish vesicular encapsulation or functional delivery. Evidence for dietary cross-kingdom regulation remains mixed. Although plant extracellular small RNAs can regulate fungal pathogens and ginger-derived particle-associated small RNAs have been linked to bacterial and host responses, reproducible systemic delivery of physiologically effective plant miRNAs after normal dietary intake has not been established. Lipids, proteins, metabolites, and other RNAs may also contribute to reported effects. Future studies should distinguish naturally secreted EVs, EV-like nanoparticles, and engineered nanovectors, and should combine rigorous particle characterization, RNA localization, absolute quantification, physiologically relevant dosing, and loss-of-function and rescue experiments. Such standards are essential for defining biological relevance and therapeutic potential.