Zhang Qing, Shen Yan, Zhang Chengyuan, Zhang Hanyi, Li Xuemei, Yang Shengqian, Dai Chen, Yu Xiuyan, Lou Jie, Feng Jinwei, Hu Chenglu, Lin Zhihua, Li Xiaohui, Zhou Xing
School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400054, PR China.
Yunnan Key Laboratory of Stem Cell and Regenerative Medicine & Rehabilitation School, Kunming Medical University, Kunming 650500, PR China.
Sci Adv. 2025 Mar 21;11(12):eadj1896. doi: 10.1126/sciadv.adj1896. Epub 2025 Mar 19.
Acute organ injuries represent 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. In addition, nMITO selectively targeted damaged endothelial cells via β-integrins and were 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 notably reduced inflammatory responses and repaired tissue damage. These findings suggest that nMITO is a promising therapeutic strategy for managing acute organ injuries.
急性器官损伤是一个重大的公共卫生问题，由炎症和线粒体功能障碍驱动，导致细胞损伤和器官衰竭。在本研究中，我们构建了中性粒细胞膜融合线粒体（nMITO），它将中性粒细胞膜蛋白的损伤靶向和抗炎特性与线粒体的细胞修复功能结合起来。nMITO有效阻断炎症级联反应并恢复线粒体功能，针对急性器官损伤的两个关键机制。此外，nMITO通过β整合素选择性靶向受损内皮细胞，并通过隧道纳米管输送到受损组织，增强其对炎症和细胞损伤的调节作用。在急性心肌损伤、肝损伤和胰腺炎的小鼠模型中，nMITO显著降低炎症反应并修复组织损伤。这些发现表明，nMITO是一种有前景的治疗急性器官损伤的策略。
