[Development of Plant-derived Extracellular Vesicle-based Therapeutic Systems]

Plants have long supported human life as medicines and as sources of oxygen and food. Plant resources have played central roles in healthcare including traditional remedies and modern drugs such as aspirin. Recently, attention has shifted beyond small molecules to include higher-order biological structures such as extracellular vesicles (EVs). Plant-derived nanoparticles (pdNPs), obtained from edible plants by mechanical processing, are approximately 100 nm in size, biocompatible, and outperform mammalian EVs due to their safety, oral availability, stability, and low production cost. These features highlight the potential of pdNPs as platforms for drug delivery and therapeutic applications. Our group has focused on grains, legumes, and agro-industrial byproducts such as rice bran as sources of pdNPs. Corn-derived nanoparticles (cNPs) are abundant and enriched in carotenoids including lutein and zeaxanthin. We have demonstrated that cNPs could inhibit colon26 tumor cell growth by inducing G2 arrest and apoptosis, and also activate macrophages, suggesting dual antitumor and immunostimulatory effects. Furthermore, PEGylation improved pharmacokinetics, enhancing tumor accumulation, and therapeutic efficacy after intravenous administration. Rice bran-derived nanoparticles (rbNPs), prepared at high yield from low-value biomass, showed stronger tumor-specific growth inhibition than Doxil^®, a clinically used liposomal formulation of doxorubicin, inducing apoptosis in colon26 cells and suppressing peritoneal dissemination in vivo. These findings highlight the potential of rbNPs as sustainable nanomedicines with therapeutic activity and environmental value. In conclusion, pdNPs, particularly cNPs and rbNPs, are cost-effective, safe, and sustainable biomaterials with great potential for advancing cancer therapy, vaccine development, and drug delivery systems.