Conjugation of a photosensitizer to an oligoarginine-based cell-penetrating peptide increases the efficacy of photodynamic therapy

ChemMedChem. 2006 Apr;1(4):458-63. doi: 10.1002/cmdc.200500036.

Abstract

To improve the efficiency of intracellular delivery of photosensitizers and the efficacy of photodynamic therapy, a membrane-penetrating arginine oligopeptide (R7) was conjugated to 5-[4-carboxyphenyl]-10,15,20-triphenyl-2,3-dihydroxychlorin (TPC). The resulting conjugate (R7-TPC) enhanced intracellular TPC uptake, which increased proportionally with the incubation time of the conjugate. The water solubility of the highly hydrophobic TPC photosensitizer was also improved after conjugation. Increased phototoxicity of R7-TPC was observed after an incubation time of only 30 min. Tumor cells mainly underwent apoptosis at lower concentrations of the photosensitizer-polyarginine conjugate, whereas necrotic cell damage became prevalent at higher concentrations.

Publication types

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

MeSH terms

  • Arginine / chemistry*
  • Arginine / therapeutic use*
  • Cell Line, Tumor
  • Humans
  • Microscopy, Confocal
  • Oligopeptides / chemistry*
  • Oligopeptides / therapeutic use*
  • Photochemotherapy*
  • Photosensitizing Agents / chemistry*
  • Photosensitizing Agents / therapeutic use*
  • Spectrophotometry, Ultraviolet

Substances

  • Oligopeptides
  • Photosensitizing Agents
  • Arginine