Carbon Dot Nanozymes with Ferrous Ion‐Chelating and Antioxidative Activity Inhibiting Ferroptosis to Alleviate Renal Ischemia‐Reperfusion Injury

Abstract Renal ischemia‐reperfusion (I/R) significantly contributes to acute kidney injury (AKI), causing substantial oxidative stress and metabolic disruptions. Ferroptosis, a Fe 2+ ‐dependent form of regulated cell death characterized by lipid peroxide accumulation, is the predominant cause of renal I/R injury (RIRI). Here, carbon dot (C‐dot) nanozymes that inhibit ferroptosis by regulating Fe 2 ⁺ levels and scavenging reactive oxygen species, offering a potential treatment for RIRI are reported. C‐dots chelate Fe 2 ⁺ via surface carbonyl, hydroxyl, and carboxyl groups to reduce free Fe 2 ⁺ levels, suppress the Fenton reaction, and limit hydroxyl radical generation. Additionally, C‐dots scavenge superoxide anions and hydroxyl radicals to restore redox balance. By targeting the kidneys, C‐dots effectively reduce renal iron overload and lipid peroxidation to prevent ferroptotic cell death in the renal I/R male mice model. RNA sequencing (RNA‐seq) analysis further confirms the crucial roles of C‐dots in mitigating oxidative stress, preserving iron homeostasis, and downregulating acyl‐CoA synthetase long‐chain family member 4 (ACSL4) after I/R. This work emphasizes the perfect alignment between the multifunctional roles of C‐dots and the conditions required for inhibiting ferroptosis and offers an innovative strategy to treat RIRI effectively.