Catalytically Self‐Supplied Oxygen to Alleviate Hypoxia for Treatment of Acute Kidney Injury

Abstract Overcoming hypoxia is an urgent clinical challenge in acute kidney injury (AKI) treatment. Specifically, hypoxia upregulates xanthine oxidase (XO) expression and induces reactive oxygen species (ROS) generation, which exacerbates renal injury. Herein, a therapeutic strategy of self‐supply oxygen for highly efficient AKI therapy is developed, in which the biocompatible CeO 2 nanorods modified by poly(ethylene glycol)‐folic acid conjugate (CeFA) catalytically convert ROS into oxygen and effectively relieve hypoxia in injured renal tissues. Modification with poly(ethylene glycol)‐folic acid conjugate allows the catalysts to be accumulated in injured renal tissues, and the high activity of CeFA guaranteed long‐lasting endogenous ROS decomposition to continuously supply oxygen. This resulted in the relief of renal hypoxia, which inhibits XO expression, reduces ROS generation and thereafter essentially alleviates kidney injury. Moreover, CeFA significantly reduces lipopolysaccharide‐induced ROS injury and reverses hypoxia in the murine AKI model, where the levels of kidney function indicators remain normal, and inflammation is alleviated without negative effects. This study offers a promising strategy for relieving hypoxia and protecting the kidney from AKI. This methodology is anticipated to provide a valuable approach for treating other oxygen‐dependent diseases and events, such as tumors and stroke.