Renal-Clearable and Mitochondria-Targeted Metal-Engineered Carbon Dot Nanozymes for Regulating Mitochondrial Oxidative Stress in Acute Kidney Injury

Mitochondrial dysfunction-induced oxidative stress is a key pathogenic factor in acute kidney injury (AKI). Despite this, current mitochondrial-targeted antioxidant therapies have shown limited efficacy in clinical settings. In this study, we introduce a novel renal-clearable and mitochondria-targeted antioxidant nanozyme (TPP@RuCDzyme) designed to precisely modulate mitochondrial oxidative stress and mitigate AKI progression. TPP@RuCDzyme was synthesized by integrating ruthenium-doped carbon dots (CDs) with triphenylphosphine (TPP), a mitochondria-targeting moiety. This nanozyme system exhibits cascade enzyme-like activities, mimicking superoxide dismutase (SOD) and catalase (CAT), to efficiently convert cytotoxic superoxide (O 2 • - ) and hydrogen peroxide (H 2 O 2 ) into non-toxic water (H 2 O) and oxygen (O 2 ). This dual-enzyme mimicry effectively alleviates mitochondrial oxidative damage, restores mitochondrial function, and inhibits apoptosis. Compared to RuCDzyme alone, TPP@RuCDzyme demonstrated significantly enhanced efficacy in alleviating glycerol-induced AKI by inhibiting oxidative stress. By leveraging the catalytic activity derived from the integration of CDs and a metallic element, this study presents a promising therapeutic strategy for AKI and other renal diseases associated with mitochondrial dysfunction.