Catalytic Tunable Black Phosphorus/Ceria Nanozyme: A Versatile Oxidation Cycle Accelerator for Alleviating Cisplatin‐Induced Acute Kidney Injury

Oxidative stress is one leading inner cause of acute kidney injury (AKI) induced by cisplatin (DDP). Therefore, inhibiting oxidative stress is an important strategy to prevent the occurrence of DDP-induced AKI. Herein, a pH-selective "oxidative cycle accelerator" based on black phosphorus/ceria catalytic tunable nanozymes (BP@CeO₂ -PEG) to effectively and persistently scavenge ROS for alleviating DDP-induced AKI is demonstrated. The BP@CeO₂ -PEG nanozymes show pH-dependent multi-enzymatic activities, which are beneficial for selectively scavenging the excess ROS in renal tissues. In the neutral environment of kidneys, BP@CeO₂ -PEG nanozymes can accelerate its catalytic "oxidative cycle" by increasing the ratio of Ce³⁺ /Ce⁴⁺ and improving the regeneration of ATP, effectively removing DDP-induced ROS. In addition, BP@CeO₂ -PEG nanozymes can suppress the oxidative stress-triggered renal tubular epithelial cell apoptosis by inhibiting the PI3K/Akt signaling pathway. However, in the acidic environment of cancers, the presence of H⁺ inhibits the conversion of Ce⁴⁺ to Ce³⁺ , which in turn disrupts the oxidative cycle, resulting in the loss of ROS scavenging ability and ensuring the antitumor effect of DDP. Conclusively, the nanozymes offer an excellent antioxidant for alleviating cisplatin-induced AKI and extensive use in other ROS-based injuries.