Hybrid nanovesicles derived from grapes and tomatoes with synergistic antioxidative activity.

Edible plants, rich in antioxidant compounds, offer defense against oxidative stress-induced cellular damage. However, the antioxidative benefits of edible plant-derived molecules are limited due to their instability, poor solubility, and low bioavailability. Plant-derived nanovesicles (PDNVs) have emerged as the next-generation nanotherapeutics and delivery platforms; yet, challenges including low purity, significant heterogeneity, insufficient enrichment of bioactive component and compromised therapeutic efficacy limit their application. In this study, a solvent-assisted vesicle hybridization technique was developed to engineer hybrid plant-derived nanovesicles (PDNVs), exemplified by grape and tomato-derived nanovesicles (GT-HNVs), which outperform their natural counterparts. The GT-HNVs demonstrated superior stability, enhanced radical-scavenging capabilities, and greater cellular uptake efficiency. Notably, GT-HNVs significantly reduced reactive oxygen species (ROS) levels and improved antioxidative enzyme activities in L-02 cells. Moreover, they mitigated oxidative stress-induced mitochondrial damage, restoring the membrane potential and morphology. Collectively, these findings underscore the therapeutic potential of hybrid PDNVs and offer an innovative strategy for their future research.