Enzyme-activated fluorescent probe targeting γ-glutamyl transferase for imaging and diagnosing unilateral renal injury.

The growing incidence of kidney injury and chronic kidney disease emphasizes the urgent need for effective diagnostic tools. γ-Glutamyl transferase (GGT) is a key enzyme located in the brush border of renal proximal tubules. It plays a critical role in glutathione metabolism and oxidative stress regulation and is an emerging biomarker for renal injury. In this study, we synthesized a novel fluorescent probe (DCIN-GGT) using 4-(dicyanomethylene)-2-isophorone naphthylamine (DCIN) as the fluorophore and glutamic acid as the recognition group. The detection mechanism was based on GGT-mediated hydrolysis and subsequent fluorescence activation. Validation experiments demonstrated that DCIN-GGT had excellent selectivity and sensitivity, and a low detection limit of 3.93 U/L. Furthermore, the probe could effectively distinguish between normal renal tubular epithelial cells and inflammatory or injured cells in vitro. Importantly, DCIN-GGT was successfully employed in fluorescence imaging in a unilateral ureteral obstruction (UUO) mouse model and differentiated the injured kidney from the contralateral kidney. Collectively, these results indicate that DCIN-GGT is a sensitive and reliable tool for monitoring renal GGT activity, with potential for early diagnosis and evaluation of kidney injury.