Natural Product-Derived Vesicles in Nanotherapeutics.

Natural product-derived vesicles (NPVs) are lipid bilayer-enclosed nanovesicles isolated from diverse sources, including plants, fungi, and marine organisms, and are increasingly recognized as an emerging class of extracellular vesicles with potential therapeutic relevance. Their abundance, renewability, and capacity to transport endogenous metabolites and exogenous cargoes highlight their potential as scalable biological delivery vehicles. NPVs can interact with mammalian cells, participate in intercellular communication, and influence conserved biological pathways that modulate disease, support tissue repair, and maintain cellular homeostasis. In addition, their structural plasticity provides opportunities for physicochemical optimization to improve functional performance and targeting properties. However, the development and translation of NPVs are constrained by challenges, including heterogeneity, variability in isolation procedures, and insufficient physicochemical and functional characterization. This review presents a systematic framework encompassing source identification, purification strategies, and characterization methods, while integrating separation approaches with multifaceted assessments to facilitate the rational development of NPVs, with particular emphasis on recent advances in structural optimization and therapeutic efficacy. Furthermore, the status of nine clinical trials is highlighted, reflecting the growing translational and therapeutic potential of NPVs. By delineating current limitations and discussing potential solutions, this review provides practical guidance for improving the physicochemical consistency and biological performance of NPVs, thereby facilitating their development as nature-inspired nanotherapeutic systems.