A KIM-1 targeted ONOO^--sensitive NIR fluorescence probe for enhanced acute kidney injury diagnosis

Acute kidney injury (AKI) is a swiftly advancing condition that may result in kidney failure and pose a significant threat to life. Therefore, diagnosis of AKI is crucial for treating AKI and preventing the worsening of the condition. We developed a near-infrared fluorescent probe, CyO@CD-Ser, designed for the diagnosis of AKI. This probe targets kidney injury molecule-1 (KIM-1) and is activated by ONOO^-. It consists of l-serine-modified β-cyclodextrin and compound CyO. In this system, ONOO^-, a novel biomarker for AKI, triggers the oxidation of CyO to produce compound CyOH, resulting in a pronounced enhancement of near infrared fluorescence, offering a clear, visual signal for the detection of AKI. Through its modification with l-serine, β-cyclodextrin is able to efficiently penetrate cells by targeting KIM-1 receptors, thereby enhancing its specificity and effectiveness. In vitro and in vivo experiments demonstrate the probe's high sensitivity and biocompatibility, with a detection limit of 42.7 nM for ONOO^-. Fluorescence is detectable in cisplatin-induced AKI after 12 h, becoming significant at 24 h. This suggests that CyO@CD-Ser can identify AKI earlier than traditional methods, offering a valuable tool for studying and diagnosing drug-induced AKI. Consequently, the probes we constructed can detect AKI early by precisely targeting and identifying biomarkers, preventing the deterioration of the condition, and providing an opportunity for early treatment for patients.