Anti-Inflammatory Artificial Extracellular Vesicles with Notable Inhibition of Particulate Matter-Induced Skin Inflammation and Barrier Function Impairment

Particulate matter (PM) exposure disrupts the skin barrier, causing cutaneous inflammation that may eventually contribute to the development of various skin diseases. Herein, we introduce anti-inflammatory artificial extracellular vesicles (AEVs) fabricated through cell extrusion using the biosurfactant PEGylated mannosylerythritol lipid (P-MEL), hereafter named AEV_P‑MEL. The P-MEL has anti-inflammatory abilities with demonstrated efficacy in inhibiting the secretion of pro-inflammatory mediators. Mechanistically, AEV_P‑MEL enhanced anti-inflammatory response by inhibiting the mitogen-activated protein kinase (MAPK) pathway and decreasing the release of inflammatory mediators such as reactive oxygen species (ROS), cyclooxygenase-2 (COX-2), and pro-inflammatory cytokines in human keratinocytes. Moreover, AEV_P‑MEL promoted increased expression levels of skin barrier proteins (e.g., involucrin, IVL) and water–proteins (e.g., aquaporin 3, AQP3). In vivo studies revealed that repeated PM exposure to intact skin resulted in cutaneous inflammatory responses, including increased skin thickness (hyperkeratosis) and mast cell infiltration. Importantly, our data showed that the AEV_P‑MEL treatment significantly restored immune homeostasis in the skin affected by PM-induced inflammation and enhanced the intrinsic skin barrier function. This study highlights the potential of the AEV_P‑MEL in promoting skin health against PM exposure and its promising implications for the prevention and treatment of PM-related skin disorders.