A highly selective fluorescent probe for real-time imaging of UDP-glucuronosyltransferase 1A8 in living cells and tissues

Abstract

Uridine diphosphate (UDP)-glucuronosyltransferases (UGTs) are enzymes involved in the biotransformation of important endogenous compounds such as steroids, bile acids, and hormones as well as exogenous substances including drugs, environmental toxicants, and carcinogens. Here, a novel fluorescent probe BDMP was developed based on boron-dipyrromethene (BODIPY) with high sensitivity for the detection of UGT1A8. The glucuronidation of BDMP not only exhibited a red-emission wavelength (λ_ex/λ_em = 500/580 nm), but also displayed an excellent UGT1A8-dependent fluorescence signal with a good linear relationship with UGT1A8 concentration. Based on this perfect biocompatibility and cell permeability, BDMP was successfully used to image endogenous UGT1A8 in human cancer cell lines (LoVo and HCT15) in real time. In addition, BDMP could also be used to visualize UGT1A8 in tumor tissues. These results suggested that BDMP is a promising molecular tool for the investigation of UGT1A8-mediated physiological function in humans.

Graphical abstract

Keywords

UDP-glucuronosyltransferase 1A8 / fluorescent probe / subtype selectivity / fluorescence imaging

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Declaration of competing interest

All the authors declare no competing financial interest.

Acknowledgments

The authors thank the Natural Science Foundation of Liaoning Province 2020-MS-252 and the National Key R&D Program of China (Grant No. 2018YFC1603001).

Electronic Supplementary Material

Supplementary material is available in the online version of this article at https://dx.doi.org/10.1007/s11705-021-2064-8 and is accessible for authorized users.

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