Phenolic‐Rich Grape Exosome‐Like Nanoparticles: Evidence of Multivesicular Body Pathway Secretion and Therapeutic Effect on Oral Inflammation

Grapes, a widely consumed fruit, are rich in bioactive phenolic compounds with demonstrated anti-inflammatory properties. Exosomes carry a diverse array of bioactive molecules derived from their parent cells. In recent years, Plant-derived exosome-like nanoparticles (PLENs) have garnered significant research interest due to their unique biological properties and therapeutic potential. We have successfully isolated and characterized grape exosome-like nanoparticles (GELNs) with ideal size (~160 nm) and bilayer membrane structure from Kyoho grapes. Through proteomics combined with in situ TEM analyses, we provide direct evidence that GELNs are formed and secreted via the multivesicular body (MVB) pathway. The metabolomics analysis revealed that GELNs contained higher levels of phenolic compounds and lower carbohydrate content compared to grape juice. Applying GELNs to inflammation reduces the level of inflammatory factors in the tissue and relieves the inflammatory response. Notably, GELNs exhibit low toxicity and remarkable storage stability. Our study presents a novel non-toxic nanotherapeutic strategy for oral inflammation that can effectively reduce the inflammatory response.