β-Glucuronidase(GUS)plays a key role in tumor initiation,metastasis,and progression,and thus,has been proposed as a promising cancer biomarker.In this study,we designed an enzyme-activatable near-infrared(NIR)fluores...β-Glucuronidase(GUS)plays a key role in tumor initiation,metastasis,and progression,and thus,has been proposed as a promising cancer biomarker.In this study,we designed an enzyme-activatable near-infrared(NIR)fluorescent probe(DCM-βGlcA)for the rapid and accurate detection of GUS activity in vitro,in vivo and ex vivo.The DCM-βGlcA was prepared by linking a glucuronic acid residue to dicyanomethylene-4 H-pyran(DCM).This probe exhibited significant light-up NIR fluorescent signals at 680 nm after reacting with GUS and the Stokes shift could reach 150 nm.The DCM-βGlcA showed a high sensitivity toward GUS and an excellent linear relationship at concentrations ranging between 0 and 4 U L^(-1)(R^(2)=0.9974)with the limit of detection as low as 0.19 U L^(-1).We used the DCM-βGlcA to identify GUS serum levels in both cancer patients and healthy individuals with a similar accuracy as that of an enzyme-linked immunosorbent assay(ELISA)while being easier and faster to perform.Moreover,the DCM-βGlcA was used for tracking endogenous GUS in living cells,thereby discriminating GUSoverexpressed liver cancer from normal cells.Additionally,the DCM-βGlcA was able to detect and image endogenous GUS in liver cancer tissue and tumor-bearing mouse models.These findings demonstrate the potential of the DCM-βGlcA as a promising tool for detecting and monitoring GUS activity in preclinical applications.展开更多
基金supported by the National Natural Science Foundation of China(81801858)China Postdoctoral Science Foundation(2018M641676)the Applied Basic Research Program of Shanxi Province(201801D221408)。
文摘β-Glucuronidase(GUS)plays a key role in tumor initiation,metastasis,and progression,and thus,has been proposed as a promising cancer biomarker.In this study,we designed an enzyme-activatable near-infrared(NIR)fluorescent probe(DCM-βGlcA)for the rapid and accurate detection of GUS activity in vitro,in vivo and ex vivo.The DCM-βGlcA was prepared by linking a glucuronic acid residue to dicyanomethylene-4 H-pyran(DCM).This probe exhibited significant light-up NIR fluorescent signals at 680 nm after reacting with GUS and the Stokes shift could reach 150 nm.The DCM-βGlcA showed a high sensitivity toward GUS and an excellent linear relationship at concentrations ranging between 0 and 4 U L^(-1)(R^(2)=0.9974)with the limit of detection as low as 0.19 U L^(-1).We used the DCM-βGlcA to identify GUS serum levels in both cancer patients and healthy individuals with a similar accuracy as that of an enzyme-linked immunosorbent assay(ELISA)while being easier and faster to perform.Moreover,the DCM-βGlcA was used for tracking endogenous GUS in living cells,thereby discriminating GUSoverexpressed liver cancer from normal cells.Additionally,the DCM-βGlcA was able to detect and image endogenous GUS in liver cancer tissue and tumor-bearing mouse models.These findings demonstrate the potential of the DCM-βGlcA as a promising tool for detecting and monitoring GUS activity in preclinical applications.
