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. Although small molecule antioxidant drugs are used to reduce the occurrence of DDP-induced AKI in clinics, it comes at the cost of reducing the anticancer effects of DDP. Herein, we demonstrated 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. The BP@CeO2-PEG nanozymes showed pH-dependent multi-enzymatic activities, which were beneficial for selectively scavenging the excess ROS in renal tissues. In the neutral environment of kidneys, BP@CeO2-PEG nanozymes could 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 could 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+ inhibited the conversion of Ce4+ to Ce3+, which in turn disrupted 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 extensively using in other ROS-based injuries. This article is protected by copyright. All rights reserved.