Precision‐Engineered Silver Single‐Atom Carbon Dot Nanozymes for Theranostic Management of Acute Kidney Injury

ABSTRACT Overproduction of reactive oxygen species (ROS) is a key pathogenic feature in acute kidney injury (AKI), leading to rapid decline in renal function with high mortality rates that call for effective antioxidant therapies. Herein, we present triphenylphosphonium‐functionalized carbon dots supported by single‐atom silver (T‐Ag _SA ‐CDs) that integrate fluorescent antioxidant nanozymes for the accurate ROS scavenging and real‐time bioimaging of AKI. By anchoring silver in single‐atom and sub‐nanocluster states on a carbon dot matrix, T‐Ag _SA ‐CDs exhibit exceptional superoxide dismutase (SOD)‐ and glutathione peroxidase (GPx)‐like activities, surpassing traditional nanozymes in ROS neutralization efficiency. Density functional theory (DFT) calculations disclose a low‐energy reaction pathway common to both nitrogen‐doped carbon dots (N‐CDs) and Ag _SA ‐CDs, clarifying the mechanism behind their dual SOD‐ and GPx‐mimetic activities. The biocompatible N‐CDs platform guarantees the stability, minimizes Ag ⁺ ‐associated toxicity, and enhances catalytic performance through synergistic Ag _SA ‐CD interactions. Targeting mitochondria through triphenylphosphonium functionalization facilitates site‐specific antioxidant protection, demonstrating robust therapeutic efficacy in a cisplatin‐induced AKI mouse model. Additionally, the intrinsic fluorescence of T‐Ag _SA ‐CDs facilitates non‐invasive monitoring of biodistribution and renal accumulation, promotes the recovery of damaged kidney tissue, alleviates oxidative stress and post‐cure assessment, and offers a self‐reported theranostic platform, while also aiming to improve its clinical application.