Gold Cluster-Based Profiling of Early Stage Acute Kidney Injury through Second Near-Infrared Fluorescence Imaging and Mass Spectrometry Imaging

Acute kidney injury (AKI) poses a major challenge due to the rapid deterioration of renal function, for which the optimal intervention timing has already passed until clinical diagnostics sense abnormalities. Meanwhile, the lack of means to visually understand early-stage AKI at the molecular level hinders the development of interventive strategies. Herein, we developed a high-orthogonal dual-mode imaging strategy integrating second near-infrared (NIR-II) fluorescence imaging and mass spectrometry imaging (MSI) based on gold clusters for profiling early-stage AKI. Through fabrication and screening, we obtained β-cyclodextrin-capped gold clusters (CD-AuNCs) demonstrating stable NIR-II fluorescence emission, satisfactory ionizing capability, the renal-excreted route, and excellent biocompatibility. Following intravenous injection, CD-AuNCs rapidly (as soon as 5 min post injection) and sensitively sensed the subtle abnormal variation of renal functions during AKI to exhibit differential renal-excreted behaviors. This achieved much earlier detection of AKI by NIR-II fluorescence imaging in a noninvasive real-time manner than invasive clinically adopted blood testing (at least 22 h earlier) and histopathological examination (at least 4 h earlier). Furthermore, CD-AuNCs-based MSI enabled molecular-level investigation of early-stage AKI, visually identifying key endogenous lipids that were remodeled in the renal cortex and medulla. In view of the excellent biocompatibility and easily scalable one-pot synthesis of CD-AuNCs, our strategy holds the potential for clinical translation.