Redox‐Mediated Artificial Non‐Enzymatic Antioxidant MXene Nanoplatforms for Acute Kidney Injury Alleviation

Zhao, Xing; Wang, Li‐Ya; Li, Jia‐Meng; Peng, Li‐Mei; Tang, Chun‐Yan; Zha, Xiang‐Jun; Ke, Kai; Yang, Ming‐Bo; Su, Bai‐Hai; Yang, Wei

Acute kidney injury (AKI), as a common oxidative stress‐related renal disease, causes high mortality in clinics annually, and many other clinical diseases, including the pandemic COVID‐19, have a high potential to cause AKI, yet only rehydration, renal dialysis, and other supportive therapies are available for AKI in the clinics. Nanotechnology‐mediated antioxidant therapy represents a promising therapeutic strategy for AKI treatment. However, current enzyme‐mimicking nanoantioxidants show poor biocompatibility and biodegradability, as well as non‐specific ROS level regulation, further potentially causing deleterious adverse effects. Herein, the authors report a novel non‐enzymatic antioxidant strategy based on ultrathin Ti(3)C(2)‐PVP nanosheets (TPNS) with excellent biocompatibility and great chemical reactivity toward multiple ROS for AKI treatment. These TPNS nanosheets exhibit enzyme/ROS‐triggered biodegradability and broad‐spectrum ROS scavenging ability through the readily occurring redox reaction between Ti(3)C(2) and various ROS, as verified by theoretical calculations. Furthermore, both in vivo and in vitro experiments demonstrate that TPNS can serve as efficient antioxidant platforms to scavenge the overexpressed ROS and subsequently suppress oxidative stress‐induced inflammatory response through inhibition of NF‐κB signal pathway for AKI treatment. This study highlights a new type of therapeutic agent, that is, the redox‐mediated non‐enzymatic antioxidant MXene nanoplatforms in treatment of AKI and other ROS‐associated diseases.