Advances in Plant-Derived Extracellular Vesicles: Implications for Apple-Derived EVs

Plant-derived extracellular vesicles (PDEVs) are nanoscale membrane vesicles released by edible plants that deliver proteins, lipids, nucleic acids, and small metabolites to recipient cells, thereby modulating inflammation, barrier function, metabolism, and intercellular signaling. In recent years, PDEV research has advanced from concept and in vitro observations to engineering-ready systems with validation in animal models, encompassing oral, transdermal, and intranasal delivery paradigms. Among edible plants, the apple has broad consumption and a favorable safety profile; however, studies on apple-derived extracellular vesicles (ADEVs) lag behind those on other plant EVs. Accordingly, this review systematically summarizes ADEV progress across extraction methods, characterization, molecular cargo, and roles in disease settings. We highlight evidence gaps in animal efficacy and translation, and propose priorities including process standardization, harmonized critical quality attributes, in vivo biodistribution, and long-term safety. Our aim is to provide a reference for ADEV research and to accelerate the development of safe, low-cost, scalable bionanocarriers for disease therapy.