Cyanine-based 1-amino-1-deoxyglucose as fluorescent probes for glucose transporter mediated bioimaging

Biochem Biophys Res Commun. 2016 May 27;474(2):240-246. doi: 10.1016/j.bbrc.2016.03.133. Epub 2016 Mar 28.

Abstract

Two novel cyanine-based 1-amino-1-deoxy-β-glucose conjugates (Glu-1N-Cy3 and Glu-1N-Cy5) were designed, synthesized and their fluorescence characteristics were studied. Both Glu-1N-Cy3 and Glu-1N-Cy5 accumulate in living HT29 human colon cancer cells, which overexpress glucose transporters (GLUTs). The cellular uptake of the bioprobes was inhibited by natural GLUT substrate d-glucose and 2-deoxy-d-glucose. The GLUT specificity of the probes was validated with quercetin, which is both a permeant substrate via GLUTs and a high-affinity inhibitor of GLUT-mediated glucose transport. Competitive fluorometric assay for GLUT substrate cell uptake revealed that Glu-1N-Cy3 and Glu-1N-Cy5 are 5 and 10 times more sensitive than 2-NBDG, a leading fluorescent glucose bioprobe. This study provides fundamental data supporting the potential of these two conjugates as new powerful tools for GLUT-mediated theranostics, in vitro and in vivo molecular bioimaging and drug R&D.

Keywords: Cyanine-based glycoconjugate; Fluorescent probe; Fluorometric competition; Glucose transporter.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbocyanines / chemical synthesis*
  • Fluorescent Dyes / chemical synthesis
  • Glucose / chemistry
  • Glucose / pharmacokinetics
  • Glucose Transport Proteins, Facilitative / metabolism*
  • Image Enhancement / methods
  • Microscopy, Fluorescence / methods*
  • Molecular Imaging / methods*
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Subcellular Fractions / metabolism*

Substances

  • Carbocyanines
  • Fluorescent Dyes
  • Glucose Transport Proteins, Facilitative
  • cyanine dye 3
  • cyanine dye 5
  • Glucose