Real-time monitoring of γ-Glutamyltranspeptidase in living cells and in vivo by near-infrared fluorescent probe with large Stokes shift

Abstract

γ-Glutamyltranspeptidase (GGT) is a cell surface-bound enzyme that is closely implicated in various physiological disorders such as tumor. Thus, an efficient method for monitoring GGT is extremely important for biological studies and disease diagnosis. Herein, a near-infrared fluorescent probe (TMN-Glu) has been developed for turn-on trapping of GGT activity in vitro and in vivo based on conjugating a dicyanoisophorone derivative fluorophore with a GGT activatable γ-glutamyl amide moiety. Advantages of the probe include near-infrared emission (658 nm), with large Stokes shift (213 nm), high specificity, high sensitivity (LOD = 0.024 U/L), low cytotoxicity and high imaging resolution, allowing for the real-time imaging endogenous GGT in living cells. Probe TMN-Glu was highly feasible to report on the GGT levels in different types of cells. Notably, we also demonstrated its applicability in real-time visualizing endogenous GGT in tumor-bearing nude mice with low background interference. These results indicated that the probe held great promise for real-time sensing and tracking GGT in complex biological systems, which would be useful for basic researches and clinical diagnosis of GGT-related diseases.