A sulfonate-modified Activatable probe for in vivo imaging and urinalysis of renal GGT activity in diabetic nephropathy

Diabetic nephropathy (DN) represents a major complication of diabetes, where the early detection of renal dysfunction remains challenging due to the lack of sensitive and non-invasive biomarkers. This study reports the rational design and comprehensive evaluation of GGT-SO3, a novel activatable near-infrared fluorescent and photoacoustic probe, for the specific sensing of γ-glutamyl transpeptidase (GGT), an enzyme implicated in oxidative stress and disease progression. The probe demonstrated exceptional selectivity, low cytotoxicity, and a favorable dual hepatic-renal clearance profile. In a streptozotocin (STZ)-induced murine model of progressive diabetes, in vivo photoacoustic imaging revealed a clear, stage-dependent enhancement of renal GGT-SO3 signal, which correlated with histological evidence of kidney damage. Importantly, a strong correlation was also established between disease severity and the fluorescence intensity of the activated probe metabolite excreted in urine. These findings collectively highlight GGT-SO3 as a promising tool for the non-invasive visualization and longitudinal monitoring of renal GGT activity, offering a potential new strategy for assessing diabetic nephropathy progression.