Nebulized M2 macrophage-derived nanovesicles for the treatment of explosion-induced acute lung injury

Gas explosion-induced acute lung injury (ALI) presents a significant clinical challenge in industrial and military contexts, yet current therapeutic interventions remain suboptimal. Extracellular vesicles (EVs) have emerged as promising nanoscale therapeutic agents, owing to their superior biocompatibility and inherent therapeutic potential. In this study, we engineered and isolated alternatively activated macrophages extracellular vesicles (M2-EVs) and administered them via nebulization to the injured lung tissue in an established murine model of blast-induced ALI. Administration of M2-EVs led to a significant amelioration of pulmonary function, characterized by decreased lung injury scores and attenuated inflammatory markers. Mechanistically, M2-EVs promoted the M1-to-M2 phenotypic transition of pulmonary macrophages, modulated the P62-Keap1-Nrf2 signaling pathway, and consequently mitigated excessive autophagy and oxidative stress. Collectively, these findings not only offer mechanistic insights into the pathogenesis of blast-induced ALI but also highlight M2-EVs as a promising cell-free therapeutic approach for explosion-related pulmonary injuries.