From Garden to Clinic: Plant‑Derived Exosome‑Like Nanovesicles for Precision Oxidative Stress Therapy

Tianhang Yang,1,2,* Mengjia He,1,2,* Jinxi Huang,1,2 Dan Zhang,3 Tao Song,1,2 Jun Tan,4 Xianyao Wang,1,2 Yanxin Lu,5 Qinghong Kong,6 Jidong Zhang1,2,7 1Department of Immunology, Zunyi Medical University, Zunyi, People’s Republic of China; 2Key Laboratory of Cancer Prevention and Treatment of Guizhou Province, Zunyi Medical University, Zunyi, People’s Republic of China; 3Library, Zunyi Medical University, Zunyi, People’s Republic of China; 4Department of Histology and Embryology, Zunyi Medical University, Zunyi, People’s Republic of China; 5Basic Medical Science Department, Zunyi Medical College-Zhuhai Campus, Zhuhai, People’s Republic of China; 6Guizhou Provincial College-based Key Laboratory for Tumor Prevention and Treatment with Distinctive Medicines, Zunyi Medical University, Zunyi, People’s Republic of China; 7Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine, Zunyi Medical University, Zunyi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jidong Zhang, Email [email protected] Qinghong Kong, Email [email protected]: Plant-derived exosome-like nanovesicles (PELNs) are naturally derived lipid-bilayer nanocarriers, which possess intrinsic activity to modulate oxidative stress through their diverse cargos of proteins, lipids, nucleic acids, and phytochemicals. Unlike conventional oxidative-stress interventions, PELNs achieve multifactorial, cargo-based redox regulation within a protective membrane that enhances bioavailability, preserves labile components, and improves cellular uptake while reducing off-target toxicity. Their low immunogenicity and inherent stability, together with the potential for surface modification and therapeutic co-loading, enable tissue-selective and sustained control of redox balance, including integration with biomaterial platforms such as hydrogels and scaffolds. This review synthesizes advances in PELN biogenesis, compositional characteristics, and isolation methods, and compares their biological and functional traits with mammalian exosomes. We propose an antioxidant/pro-oxidant dichotomy as a unifying mechanistic framework and highlight therapeutic prospects in oxidative stress–related disorders such as wound healing, atherosclerosis, neurodegeneration, and cancer. Translational considerations—including manufacturing scale-up, stability, biodistribution and biosafety—are critically discussed, alongside practical strategies to address these challenges. By linking mechanistic understanding with material-based engineering and application-oriented perspectives, this review establishes a materials-to-clinic roadmap for PELNs and positions them as promising next-generation nano-tools for precision oxidative-stress therapy.Keywords: plant-derived exosome-like nanovesicles, oxidative stress therapy, nanomedicine, redox regulators, drug delivery