An ROS‐Responsive CeO ₂ –Selenium Nanozyme Mitigates Renal Injury via Coordinated Ferroptosis Inhibition and Inflammation Resolution

ABSTRACT

Acute kidney injury (AKI) and chronic kidney disease (CKD), despite distinct etiologies, share a common pathological axis characterized by reactive oxygen species (ROS) burst, ferroptosis activation, and sustained inflammation. Targeting this ROS–ferroptosis–inflammation cycle represents a promising therapeutic strategy; however, current nanoplatforms are limited by insufficient responsiveness and limited capacity to regulate shared pathological mechanisms across distinct renal disease models. Here, we develop an engineered ROS‐responsive nanozyme by integrating diselenide‐bridged organosilica, hyaluronic acid (HA)‐modified cerium oxide (CeO ₂ ), and a selenium‐containing diselenide framework. Under oxidative stress, MON@HA‐CeO ₂ undergoes ROS‐triggered disassembly, coupling HA‐CeO ₂ ‐mediated ROS scavenging with selenium‐related GPX4 restoration to suppress lipid peroxidation, ferroptosis, and inflammatory amplification. In both glycerol‐induced AKI and unilateral ureteral obstruction (UUO)‐induced renal fibrosis models, the nanozyme significantly improves renal function and attenuates tissue injury, fibrosis, and inflammation. Overall, this work demonstrates a versatile strategy for targeting a shared pathological axis and provides a promising platform for the treatment of diverse renal diseases.