Target-selective phototherapy using a ligand-based photosensitizer for type 2 cannabinoid receptor

Chem Biol. 2014 Mar 20;21(3):338-44. doi: 10.1016/j.chembiol.2014.01.009. Epub 2014 Feb 27.

Abstract

Phototherapy is a powerful, noninvasive approach for cancer treatment, with several agents currently in clinical use. Despite the progress and promise, most current phototherapy agents have serious side effects as they can lead to damage to healthy tissue, even when the photosensitizers are fused to targeting molecules due to nonspecific light activation of the unbound photosensitizer. To overcome these limitations, we developed a phototherapy agent that combines a functional ligand and a near infrared phthalocyanine dye. Our target is type 2 cannabinoid receptor (CB2R), considered an attractive therapeutic target for phototherapy given it is overexpressed by many types of cancers that are located at a surface or can be reached by an endoscope. We show that our CB2R-targeted phototherapy agent, IR700DX-mbc94, is specific for CB2R and effective only when bound to the target receptor. Overall, this opens up the opportunity for development of an alternative treatment option for CB2R-positive cancers.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Indoles / chemical synthesis
  • Indoles / metabolism*
  • Indoles / pharmacology
  • Indoles / therapeutic use
  • Ligands*
  • Mice
  • Microscopy, Fluorescence
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Organosilicon Compounds / chemical synthesis
  • Organosilicon Compounds / metabolism*
  • Organosilicon Compounds / pharmacology
  • Organosilicon Compounds / therapeutic use
  • Photosensitizing Agents / chemical synthesis
  • Photosensitizing Agents / metabolism*
  • Photosensitizing Agents / pharmacology
  • Photosensitizing Agents / therapeutic use
  • Phototherapy
  • Protein Binding
  • Receptor, Cannabinoid, CB2 / antagonists & inhibitors
  • Receptor, Cannabinoid, CB2 / metabolism*

Substances

  • IR700DX-mbc94
  • Indoles
  • Ligands
  • Organosilicon Compounds
  • Photosensitizing Agents
  • Receptor, Cannabinoid, CB2