Cucumber-Derived Exosome-like Nanovesicles Encapsulating Epigallocatechin Gallate for Skin Depigmentation: Molecular Docking, Stability, and Efficacy in B16/F10 Cells and Zebrafish

Abstract

To address the challenges of instability and low bioavailability that limit the application of (-)epigallocatechin gallate (EGCG) as a whitening agent, we engineered cucumber-derived exosome-like nanovesicle (CEV) as a synergistic nanocarrier. A hybrid isolation method combining polyethylene glycol precipitation with electrophoretic dialysis (PED) was established to obtain high-purity CEVs. The resulting EGCG-loaded CEVs (EGCG@CEVs) achieved 95.43% encapsulation efficiency with enhanced stability and a sustained release profile. Metabolomics and network pharmacology identified the STAT3/MAPK signaling axis as the primary target, a mechanism subsequently validated in B16F10 melanocytes and zebrafish models.Compared with free EGCG, EGCG@CEVs significantly decreased tyrosinase activity and melanin production.With the stable EGCG@CEVs system, the ERK-STAT3-MITF pathway can be regulated, potentially functioning as a plant-based cosmetic system.