A novel triarylboron based ratiometric fluorescent probe for in vivo targeting and specific imaging of cancer cells expressing abnormal concentration of GGT

Biosens Bioelectron. 2019 Oct 1:142:111497. doi: 10.1016/j.bios.2019.111497. Epub 2019 Jul 10.

Abstract

Abnormal expression of γ-glutamyltranspeptidase (GGT) in living organisms is closely associated with tumorigenesis. However, few reported fluorescence probes can specifically respond to abnormal concentration of GGT. Here, by functionalizing triarylboron moiety with three GGT-specific substrate (GSH) units, a novel fluorescence probe, TAB-3-GSH, was developed for detecting GGT. The results showed that TAB-3-GSH selectively responds to abnormally high levels of GGT (100-1000 U/L) rather than to normal GGT levels (<100 U/L) with ratiometric readout, since the amide linkage can be further hydrolyzed under high GGT levels. TAB-3-GSH was also capable of differentiating GGT-overexpressing ovarian cancer cells from normal cells, because of an improvement in the probe's cell membrane permeability upon reaction with GGT. Moreover, the probe could achieve selective imaging of SKOV-3 tumor site in xenograft mice model. Thus, TAB-3-GSH is a promising probe for tumor targeting in vivo.

Keywords: Fluorescence; GGT; Ovarian cancers; Targeting; Triarylboron.

MeSH terms

  • Animals
  • Biosensing Techniques / methods
  • Boron Compounds / chemistry*
  • Cell Line, Tumor
  • Female
  • Fluorescent Dyes / chemistry*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Mice, Nude
  • Optical Imaging / methods*
  • Ovarian Neoplasms / diagnostic imaging
  • Ovarian Neoplasms / enzymology*
  • gamma-Glutamyltransferase / analysis*

Substances

  • Boron Compounds
  • Fluorescent Dyes
  • gamma-Glutamyltransferase