An ROS-Responsive CeO2–Selenium Nanozyme Mitigates Renal Injury via Coordinated Ferroptosis Inhibition and Inflammation Resolution

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.