Inhalable PD-L1-engineered hybrid cellular vesicles suppress excessive neutrophil activation and restore mitochondrial homeostasis to alleviate ischemia–reperfusion lung injury and pneumonia

-induced pneumonia, nebulized administration of Res-PD-L1@nmEVs significantly attenuated lung tissue damage, inhibited neutrophil activation, reduced inflammatory cytokine release, improved alveolar barrier integrity, promoted the recovery of pulmonary function, and alleviated hypoxemia. Transcriptomic analysis revealed that the treatment synergistically enhanced energy metabolism and biosynthetic processes while suppressing inflammatory pathways. This study presents a comprehensive targeted strategy that simultaneously addresses immune dysregulation, oxidative damage, and metabolic dysfunction in inflammatory lung diseases, demonstrating significant potential for clinical translation.