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

Renal ischemia-reperfusion (I/R) significantly contributes to acute kidney injury (AKI), causing substantial oxidative stress and metabolic disruptions. Ferroptosis, a Fe2+-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 Fe2⁺ levels and scavenging reactive oxygen species, offering a potential treatment for RIRI are reported. C-dots chelate Fe2⁺ via surface carbonyl, hydroxyl, and carboxyl groups to reduce free Fe2⁺ 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.