Specific fluorescence release based on synergistic activation of enzymes and position-dependent of electrophilic groups to diagnose intrahepatic cholestasis of pregnancy

Abstract

The early diagnosis and effective treatment of disease have presented new challenges to today's researchers. Recently, an important direction of the development of the fluorescent probes field is to provide convenient detection tools for clinical diagnosis. Intrahepatic cholestasis of pregnancy (ICP), a pregnancy-specific liver disease associated with poor maternal and fetal outcome, lack biochemical diagnosis indicator with relatively high specificity. Glutathione S-transferases may be a potential candidate for ICP diagnosis owing to their high concentrations in the liver, however, fluorescent detection tool for GSTs with high selectivity is scarce, owing to the interference of high non-enzymatic reaction with GSH. In this work, a probe (MB5) through fine structure regulation for specific fluorescence response GSTs was obtained with synergistic activation of enzymes and position-dependent of electrophilic groups. Furthermore, overexpressed GSTs were visualized directly in cholestatic mice models through in vivo imaging, isolated organ imaging, and tissue slice analysis. More importantly, the serum samples of the ICP patients hold significantly high levels of GSTs concentrations, compared with healthy pregnant women. Therefore, a novel diagnostic tool and excellent detection method for ICP were provided, which will promote to the establishment of new biochemical markers of liver function in pregnancy.