Therapeutic potential of plant-derived exosome-like nanovesicles as a phytomedicine in age-related diseases

Plant-derived exosome-like nanovesicles (PDEVs) are emerging as breakthrough platforms for the treatment of age-related diseases (ARDs). These endogenous nanocarriers contain a variety of bioactive molecules, including microRNAs, proteins, lipids, and phytochemicals, which play crucial roles in therapy. PDEVs have strong potential to treat chronic inflammation, oxidative stress, cellular senescence, and mitochondrial dysfunction, all of which are related to aging. Their pleiotropic effects support wide therapeutic applications in neurodegenerative, cardiovascular, and metabolic diseases; sarcopenia; cachexia; and skin ageing. PDEVs have several advantages over synthetic nanoparticles and mammalian exosome-like nanovesicles, including good biocompatibility, low immunogenicity, and excellent in vivo stability. Being of natural origin, they can be produced on a large scale at low cost, and drugs can be effectively delivered via various routes, including oral, intravenous, and intramuscular routes. However, translating PDEVs into the clinic presents several challenges, including mass production, batch-to-batch consistency, standardized isolation and characterization methods, and regulatory issues. By combining natural plant compounds with modern nanomedicines, safe, effective, and targeted therapies for complex ARDs can be developed. However, oral delivery faces key limitations due to gastrointestinal barriers, including acidic pH, enzymatic degradation, bile salts, and mucus layers, which can compromise vesicle stability and bioavailability. Variability in intestinal uptake and microbiota interactions further affects therapeutic consistency. Protective strategies, including encapsulation, enteric coating, and surface engineering, may enhance stability and absorption. Emerging approaches such as ligand-functionalized PDEVs, hybrid nanovesicles, and stimuli-responsive delivery systems offer safer and more precise therapeutic options, improving targeting, controlled release, and translational potential.