An all‐in‐one fucosylated gold nanocluster probe enables NIR‐II imaging and multi‐mechanistic therapy of acute kidney injury

Acute kidney injury (AKI) remains a life‐threatening condition due to the lack of tools for early‐stage detection and effective treatment. Herein, we report a fucoside‐targeted gold nanocluster‐based theranostic probe (Au 44 MBA 26 ‐Fuc NCs) that integrates near‐infrared‐II photoluminescence (NIR‐II PL) imaging with multi‐mechanistic therapy for AKI. Leveraging its strong NIR‐II emission, the probe enables non‐invasive, real‐time visualization of injured kidneys within 3 min after intravenous injection in mice. Furthermore, the probe exerts potent therapeutic effects against AKI through its multi‐enzyme‐mimetic activities, including NADH oxidase, superoxide dismutase (SOD), and glutathione peroxidase (GPx), which collectively mitigate oxidative stress, regulate inflammation via macrophage polarization, and inhibit ferroptosis by upregulating glutathione peroxidase 4 (GPX4) and restoring mitochondrial function. Transcriptomics reveal that these effects are mediated through regulation of the ferroptosis/MAPK and FoxO pathways, enhancing ferroptosis resistance and antioxidant defense. The probe also demonstrates favorable biosafety and renal clearance. This work offers a targeted theranostic strategy for precise AKI management and advances the development of metal NCs‐based platforms for oxidative‐stress‐related diseases.