Hydrogels Treat Atopic Dermatitis by Transporting Marine-Derived miR-100-5p-Abundant Extracellular Vesicles

Atopic dermatitis (AD) is a prevalent skin disorder worldwide. However, many AD medications are unsuitable for long-term use due to low therapeutic efficacy and side effects. Extracellular vesicles (EVs) extracted from <i>Pinctada martensii</i> mucus have demonstrated therapeutic efficacy in AD. It is hypothesized that EVs may exert their activity on mammalian cells through their specific contents. In this study, we analyzed the results of miRNA sequencing of the EVs and investigated the potency of highly expressed miR-100-5p in treating AD. To enhance the therapeutic efficiency of the EVs in AD, we developed oxidized sodium alginate (OSA)-carboxymethyl chitosan (CMCS) self-cross-linked hydrogels as a vehicle to deliver the EVs to BALB/c mice with dermatitis. The miR-100-5p in EVs exhibited a favorable anti-inflammatory function, while the hydrogels provided enhanced skin residency. Additionally, its efficacy in inflammation inhibition and collagen synthesis was demonstrated in in vivo experiments. Mechanistically, miR-100-5p in EVs exerted anti-inflammatory effects by inhibiting the expression of FOXO3, consequently suppressing the activation of the downstream NLRP3 signaling pathway. This study underscores the significance of utilizing OSA-CMCS hydrogels as a vehicle for delivering miR-100-5p in <i>P. martensii</i> mucus-derived EVs for the treatment of AD.