Irisin-Encapsulated Mitochondria-Targeted Biomimetic Nanotherapeutics for Alleviating Acute Kidney Injury

• Published in: Advanced science p. e2402805
• Main Authors: Zhang, Xia, Liang, Lijia, Wang, Fengxian, Jose, Pedro A, Chen, Ken, Zeng, Chunyu
• Format: Journal Article
• Language: English
• Published: Germany 09.08.2024
• Subjects: acute kidney injury; irisin; mitochondria; biomimetic nanocarriers
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.202402805

Acute kidney injury (AKI) is the sudden decrease in renal function that can be attributed to dysregulated reactive oxygen species (ROS) production and impaired mitochondrial function. Irisin, a type I membrane protein secreted by skeletal muscles in response to physical activity, has been reported to alleviate kidney damage through regulation of mitochondrial biogenesis and oxidative metabolism. In this study, a macrophage membrane-coated metal-organic framework (MCM@MOF) is developed as a nanocarrier for encapsulating irisin to overcome the inherent characteristics of irisin, including a short circulation time, limited kidney-targeting ability, and low membrane permeability. The engineered irisin-mediated biomimetic nanotherapeutics have extended circulation time and enhanced targeting capability toward injured kidneys due to the preservation of macrophage membrane proteins. The irisin-encapsulated biomimetic nanotherapeutics effectively mitigate acute ischemia-reperfusion injury by protecting mitochondrial function and modulating SOD2 levels in renal tubular epithelial cells. The present study provides novel insights to advance the development of irisin as a potential therapeutic approach for AKI.