Pheophorbide-a conjugates with cancer-targeting moieties for targeted photodynamic cancer therapy

Bioorg Med Chem. 2015 Apr 1;23(7):1453-62. doi: 10.1016/j.bmc.2015.02.014. Epub 2015 Feb 16.

Abstract

Pheophorbide-a, a non-selective photosensitizer, was conjugated with cancer-targeting moieties, such as folic acid, the CRGDLASLC peptide, the cRGDfK peptide and leuprorelin, for the purpose of targeted photodynamic cancer therapy. The cellular uptake of pheophorbide-a conjugates in cancer cells overexpressing the corresponding receptors of the targeting moieties was largely enhanced compared with that in the receptor-negative cells. In the study of in vitro photodynamic activity and selectivity of pheophorbide-a conjugates in the receptor-positive and receptor-negative cells, a pheophorbide-a conjugate, (14) with an αvβ6 ligand (CRGDLASLC) exhibited the highest selectivity in the positive FaDu cells. Targeted PDT with 14 induced cell death through apoptosis and morphological apoptosis-like characteristics. These results suggest that pheophorbide-a conjugate 14 could be utilized in selective photodynamic therapy for oral cancers primarily expressing the αvβ6 receptor.

Keywords: Apoptosis; Conjugate; Fluorescence; PDT; Pheophorbide-a.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Chlorophyll / administration & dosage
  • Chlorophyll / analogs & derivatives*
  • Chlorophyll / chemistry
  • Dose-Response Relationship, Drug
  • Drug Delivery Systems / methods*
  • Humans
  • Photochemotherapy / methods*
  • Photosensitizing Agents / administration & dosage
  • Photosensitizing Agents / chemistry*

Substances

  • Photosensitizing Agents
  • Chlorophyll
  • pheophorbide a