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

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.