Renal-Clearable Nitroreductase and Viscosity Dual-Activated Hemicyanine Probes for Precise In Vivo Kidney Disease Imaging and Diagnosis

Abstract Precise renal optical imaging is crucial for the early detection of renal cell carcinoma (RCC) and renal ischemia-reperfusion injury (IRI), as well as improving therapeutic outcomes. However, the majority of currently available fluorescent probes are preferentially taken up by the liver or only respond to a single analyte, resulting in limited accuracy in renal imaging and severely impairing their performance in renal function imaging. Herein, based on a novel “two birds with one stone” strategy, we report the renal-clearable and nitroreductase (NTR)/viscosity dual-activated fluorescent probe V-NTR for precise in vivo kidney disease imaging and diagnosis. Notably, the probe displays a remarkable 31.3-fold fluorescence enhancement upon dual stimulation by NTR and elevated viscosity, significantly improving detection specificity. In vivo NIR fluorescence imaging and in vitro urine analysis studies have collectively demonstrated that V-NTR enables precise imaging of RCC and real-time monitoring of injury induced during the early ischemic phase of renal IRI. Thus, this study not only provides a novel and reliable molecular tool for the early diagnosis and real-time monitoring of kidney diseases, but also offers a generalizable chemical design platform for the development of kidney-specific molecular imaging probes.