Topical application of Tea leaf-derived nanovesicles reduce melanogenesis by modulating the miR-828b/

Over-pigmentation of skin caused by excessive melanin production faces the challenges of limited therapeutic effects and safety, the conventional tea leaf extract (TET) for pigmentation treatment has the disadvantages of residual harmful substances, low penetration efficiency, here we propose the tea leaf-derived nanovesicles (TLNVs) as natural nanomaterials that combine bioactive components in tea leaves and exosome-like delivery advantages for targeting over-pigmentation treatment. This study extracted TLNVs from fresh tea leaves by ultracentrifugation and characterized them by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and secondary metabolites composition analysis. In vitro, TLNVs exhibited stronger radical scavenging ability and tyrosinase inhibitory effect than conventional tea leaf extract, while inhibiting B16-F10 cell proliferation and melanin synthesis. Based on these in vitro results, we further evaluated the anti-pigmentation effects of TLNVs in an uvB-induced pigmented mouse model, in which TLNVs markedly reduced epidermal melanin deposition and epidermal thickness while increasing dermal thickness and collagen volume fraction. TLNVs effectively suppressed the expression of inflammatory cytokines (TNF-α and IL-1β) and promoted melanoautophagy by upregulating LC3B and downregulating P62. Moreover, confocal laser scanning microscopy (CLSM) analysis of fluorescently labeled TLNVs confirmed their penetration ability into the deep dermis, reaching approximately 200 μm. Mechanistic studies demonstrated that miR-828b in TLNVs directly targeted