Near infrared fluorescence-based bacteriophage particles for ratiometric pH imaging

Bioconjug Chem. 2008 Aug;19(8):1635-9. doi: 10.1021/bc800188p. Epub 2008 Jul 31.

Abstract

Fluorogenic imaging agents emitting in the near-infrared are becoming important research tools for disease investigation in vivo. Often pathophysiological states such as cancer and cystic fibrosis are associated with disruptions in acid/base homeostasis. The development of optical sensors for pH imaging would facilitate the investigation of these diseased conditions. In this report, the design and synthesis of a ratiometric near-infrared emitting probe for pH quantification is detailed. The pH-responsive probe is prepared by covalent attachment of pH-sensitive and pH-insensitive fluorophores to a bacteriophage particle scaffold. The pH-responsive cyanine dye, HCyC-646, used to construct the probe, has a fluorogenic pKa of 6.2, which is optimized for visualization of acidic pH often associated with tumor hypoxia and other diseased states. Incorporation of pH-insensitive reference dyes enables the ratiometric determination of pH independent of the probe concentration. With the pH-responsive construct, measurement of intracellular pH and accurate determination of pH through optically diffuse biological tissue is demonstrated.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Bacteriophages / metabolism*
  • Fluorescence*
  • Fluorescent Dyes / chemical synthesis
  • Fluorescent Dyes / chemistry
  • Fluorescent Dyes / metabolism
  • Hydrogen-Ion Concentration
  • Intracellular Space / metabolism
  • Phantoms, Imaging

Substances

  • Fluorescent Dyes