Dual-Modality Diagnosis of Early-Stage Acute Kidney Injury via a Renal Pathological Hallmark-Responsive Nanoprobe

Acute kidney injury (AKI) is associated with high mortality and remains difficult to detect at an early-stage due to the absence of distinct symptoms. Conventional clinical biomarkers, such as blood urea nitrogen and creatinine, lack sensitivity to subtle pathological changes. While histopathological examinations are sensitive, they are invasive, tedious, and risk secondary injury. These limitations highlight the urgent need for noninvasive, sensitive, rapid, and effective diagnostic strategies for AKI. To address this, we develop a dual-modality diagnostic platform (termed PKAC) that combines second near-infrared (NIR-II) fluorescence imaging with simple colorimetric urinalysis. Specifically, PKAC is a size-transformable nanoprobe comprising cyclodextrin-capped gold nanoclusters (CD-AuNCs) for signaling, an 8-arm polyethylene glycol component for size regulation, and a KTP5 peptide for renal targeting. In healthy mice, its hydrodynamic size exceeds the glomerular filtration threshold, favoring hepatic metabolism. In AKI mice, elevated reactive oxygen species (ROS) in the injured kidneys cleave PKAC, releasing CD-AuNCs for renal excretion. The in vivo NIR-II fluorescence from liberated CD-AuNCs together with the urine colorimetric readout arising from the peroxidase-like activity provides complementary and mutually reinforcing diagnostic information. Importantly, PKAC achieves a rapid early-stage AKI diagnosis, much earlier than conventional serum markers, underscoring its translational promise.