Hydrazide d-luciferin for in vitro selective detection and intratumoral imaging of Cu(2.)

Biosens Bioelectron. 2016 Sep 15:83:200-4. doi: 10.1016/j.bios.2016.04.067. Epub 2016 Apr 22.

Abstract

Copper is an essential micronutrient involved in fundamental life processes but using a bioluminescence (BL) probe to selectively sense Cu(2+)in vitro or image Cu(2+)in vivo is still unavailable. Herein, a latent BL probe hydrazide d-luciferin (1) was rationally designed and successfully applied it for selective detection of Cu(2+)in vitro and imaging Cu(2+) in living cells and in tumors. Upon the catalysis of Cu(2+), 1 was converted to d-luciferin and turned on the BL in the presence of firefly luciferase (fLuc). In vitro tests indicated that 1 could be applied for highly selective sensing Cu(2+) within the range of 0-80μM with a limit of detection (LOD) of 39.0nM. Cell and animal experiments indicated that 1 could be applied for specific BL imaging of Cu(2+) in living cells and tumors and the BL signal of 1 was more stable and longer than that of d-luciferin. We envision that this unique probe 1 might serve as an elucidative tool for further exploration of the biological roles of Cu(2+) in physiological and pathological processes in the near future.

Keywords: (D)-luciferin; Bioluminescence; Copper ion; Imaging.

MeSH terms

  • Animals
  • Benzothiazoles / chemistry*
  • Cations, Divalent / analysis
  • Cell Line, Tumor
  • Copper / analysis*
  • Humans
  • Hydrazines / chemistry
  • Luciferases, Firefly / chemistry
  • Luminescent Agents / chemistry*
  • Luminescent Measurements / methods*
  • Mice
  • Neoplasms / diagnostic imaging*
  • Optical Imaging / methods*

Substances

  • Benzothiazoles
  • Cations, Divalent
  • D-luciferin
  • Hydrazines
  • Luminescent Agents
  • Copper
  • Luciferases, Firefly