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

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.