Immuno-engineered mitochondria for efficient therapy of acute organ injuries via modulation of inflammation and cell repair

Acute organ injuries are a major public health concern, driven by
inflammation and mitochondrial dysfunction, leading to cell damage and
organ failure. In this study, we engineered neutrophil membrane-fused
mitochondria (nMITO), which combine the injury-targeting and
anti-inflammatory properties of neutrophil membrane proteins with the
cell-repairing function of mitochondria. nMITO effectively blocked
inflammatory cascades and restored mitochondrial function, targeting both
key mechanisms in acute organ injuries. Additionally, nMITO selectively
targeted damaged endothelial cells via β-integrins and was delivered to
injured tissues through tunneling nanotubes, enhancing their regulatory
effects on inflammation and cell damage. In mouse models of acute
myocardial injury, liver injury, and pancreatitis, nMITO significantly
reduced immune dysfunction and repaired tissue damage. These findings
suggest that nMITO is a promising therapeutic strategy for managing acute
organ injuries.