Medicinal and Edible Plant-Derived Exosome-Like Nanovesicles: Promising Therapeutics and Drug Delivery Nanoplatforms.

Abstract

Medicinal and edible plant-derived exosome-like nanovesicles (MEPELNVs) have attracted considerable attention as naturally derived immunomodulatory nanoplatforms for inflammatory disease intervention, owing to their excellent biocompatibility, low immunogenicity, and abundant bioactive cargoes capable of regulating immune responses. While recent reviews have broadly surveyed plant-derived exosome-like nanovesicles (PELNVs) across diverse botanical sources or focused on general isolation technologies and drug delivery applications, a systematic synthesis that specifically centers on medicinal and edible plants and integrates isolation methodology with immunomodulatory functionality remains lacking. This review addresses this gap by concentrating on the unique dual identity of MEPELNVs that combines validated pharmacological heritage from traditional medicine with the safety profile of dietary sources, and examines how their immunomodulatory potential is shaped by upstream preparation techniques. As research has progressed, techniques for isolating and preparing these extracellular vesicles have diversified; however, significant challenges remain in improving purity, optimizing yield, and preserving their immunomodulatory and anti-inflammatory biological functions. This review comprehensively surveys current mainstream isolation and preparation methods, analyzes how each technique impacts vesicle integrity and immune-regulatory activity, and discusses their differential effects on inflammatory mediator release and immune cell functionality. Based on recent preclinical findings, we highlight the potential clinical applications of MEPELNVs in three inflammation-centric areas: first, reprogramming macrophage polarization from pro-inflammatory M1 to anti-inflammatory M2 phenotypes to alleviate chronic inflammation; second, remodeling the tumor immune microenvironment by alleviating PD-L1-mediated immunosuppression; and third, ameliorating metabolic inflammation and promoting immune homeostasis in metabolic diseases. In summary, while MEPELNVs present considerable therapeutic opportunities across anti-inflammatory, anti-tumor, and metabolic disease intervention, their clinical translation is currently hindered by substantial challenges. These include the absence of standardized isolation and quality control protocols, batch-to-batch heterogeneity in vesicle yield and cargo composition, incomplete safety and toxicological profiling, poorly understood cross-kingdom regulatory mechanisms, and underdeveloped regulatory frameworks. This review critically discusses these translational barriers and proposes actionable strategies to overcome them, offering a realistic roadmap from bench to bedside. By comprehensively evaluating existing research progress, this review aims to provide theoretical support and practical technical guidance for advancing the clinical translation of MEPELNVs as novel anti-inflammatory therapeutics, ultimately promoting their broader application in precision immune modulation and inflammatory disease management.