Plant-Derived Exosome-Like Nanoparticles: Biological Functions, Therapeutic Applications, and Translational Challenges

Abstract

Plant-derived herbal medicines remain important sources of bioactive compounds, but their clinical application is often hindered by poor bioavailability and variable pharmacokinetic profiles. Recent studies have identified plant-derived exosome-like nanoparticles (PELNs) as naturally occurring bioactive nanoparticle preparations containing proteins, lipids, small RNAs, and secondary metabolites. This review examines advances in PELN isolation, biological properties, and their therapeutic applications, with particular emphasis on immune regulation, gut-microbiota modulation, and bone homeostasis. We discuss how isolation and purification approaches affect particle characteristics and the interpretation of biological outcomes. Preclinical studies suggest that PELNs from selected plant sources may modulate osteoblast and osteoclast activities, potentially contributing to bone-remodeling balance. Certain PELN preparations have shown promising characteristics for scalable production, gastrointestinal stability, and oral administration in experimental settings, but these potential advantages are source- and method-dependent and have not been established through systematic comparisons with mammalian exosomes. Interpretation of reported bioactivity is further complicated by inconsistent particle characterization, uncertain vesicular identity and purity, and limited evidence distinguishing vesicle-associated effects from those of co-isolated compounds. Further standardization of isolation, characterization, and dosing is essential for evaluating the clinical potential of PELNs. Pharmacokinetics, biodistribution, and long-term safety also remain insufficiently investigated. Overall, PELNs offer a promising area of plant-based nanomedicine research, but their clinical utility remains to be demonstrated.

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