Milk-derived exosome-loaded SS31 as a novel strategy to mitigate UV-induced photodamage in skin.

It is widely recognized that ultraviolet (UV) radiation primarily catalyses photodamage in the skin by generating reactive oxygen species (ROS). In this study, we developed a novel antioxidant complex, Exo-SS31, by loading the antioxidant peptide SS31 (also known as MTP-131, elamipretide) into milk-derived exosomes. Our findings indicate that Exo-SS31 is an effective antioxidant capable of mitigating Human dermal fibroblast (HDF) damage induced by ultraviolet exposure, suppressing ROS production, and achieving greater therapeutic efficacy than SS31 alone. This complex can regulate the levels of superoxide dismutase (SOD) and glutathione (GSH) within the skin, inhibit the expression of proteins in pathways such as pMAPK and AP-1 triggered by UV radiation, and reduce the expression of the matrix metalloproteinases MMP1 and MMP3. Through these mechanisms, Exo-SS31 effectively prevents collagen degradation in the dermis and inhibits ultraviolet-induced photodamage. The use of milk-derived exosomes as carriers for antioxidant peptides represents a promising strategy to increase the bioavailability of peptide-based therapeutics.