Hyaluronic acid microneedle delivery of frog skin-derived small extracellular vesicles for UVR-induced photoaging repair

Photoaging-induced deterioration of skin structural integrity and barrier function represents a critical challenge in dermatological health. While small extracellular vesicles (sEVs) hold therapeutic potential, their source diversity remains underexplored. Here, we report a novel sEV, designated OA-UVR-sEV, isolated from ultraviolet irradiation (UVR)-stimulated skin secretions of the amphibian Odorrana andersonii. Characterization confirmed its typical vesicular ultrastructure and excellent biocompatibility. Integrated multi-omics analysis revealed a distinct molecular cargo profile comprising miRNAs, proteins, peptides, and small-molecule metabolites. In vitro, OA-UVR-sEV substantially reduced reactive oxygen species accumulation, UVR-associated DNA damage marker expression, and pro-inflammatory cytokines in human immortalized keratinocytes and mouse dermal fibroblasts. For in vivo delivery, we developed a hyaluronic acid microneedle system, which enabled OA-UVR-sEV to attenuate wrinkle formation, stimulate dermal collagen synthesis, improve skin hydration, and reduce transepidermal water loss in photoaged mice. Analyses in dermal fibroblasts showed that these protective effects were associated with reduced activation of the MAPK and NF-κB signaling pathways. Collectively, our results establish OA-UVR-sEV as an effective anti-photoaging agent and highlight amphibian-derived sEVs as a promising new avenue for combating skin aging.