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

5 hours ago
  • #lung injury
  • #mitochondrial homeostasis
  • #PD-L1-engineered vesicles
  • Development of inhalable PD-L1-engineered hybrid cellular vesicles (Res-PD-L1@nmEVs) to treat lung ischemia-reperfusion injury and pneumonia.
  • Res-PD-L1@nmEVs combine neutrophil membrane-derived vesicles, PD-L1-overexpressing mesenchymal stem cell extracellular vesicles, and resveratrol for multi-target therapy.
  • The system enhances pulmonary accumulation, inhibits inflammation and oxidative stress, reduces apoptosis, and restores mitochondrial integrity via PINK1-mediated mitophagy.
  • PD-L1 delivery suppresses neutrophil activation by binding to PD-1, reducing inflammatory cytokine release.
  • Effective in rat models, improving lung tissue damage, alveolar barrier integrity, and pulmonary function while alleviating hypoxemia.
  • Transcriptomic analysis shows enhanced energy metabolism and biosynthetic processes with suppressed inflammatory pathways.
  • Potential for clinical translation in treating inflammatory lung diseases by addressing immune dysregulation, oxidative damage, and metabolic dysfunction.