Metallation of pentaphyrin with Lu(III) dramatically increases reactive-oxygen species production and cell phototoxicity

Eur J Med Chem. 2011 Feb;46(2):712-20. doi: 10.1016/j.ejmech.2010.12.007. Epub 2010 Dec 14.

Abstract

Photodynamic therapy (PDT) is an emerging cancer treatment modality based on the excitation of a nontoxic photosensitizer with harmless visible light to produce reactive-oxygen species (ROS) that induce apoptosis and/or necrosis in cancer cells. As the efficacy of this therapy strongly depends of the nature of the photosensitizer, there is a great interest to develop new photoactive molecules. Here we report for the first time the synthesis, characterization and bioactivity of metal complexes between the non-aromatic expanded porphyrin, namely 20-[[4'-(Trimethylsilyl)ethoxycarbonyl]phenyl-2,13-dimethyl-3,12-diethyl-[24] iso-pentaphyrin (PCRed) and Zn(II) [Zn(II)-PCRed] or Lu(III) [Lu(III)-PCRed]. The complexation of these two diamagnetic heavy metal ions to PCRed improved the properties of the free photosensitizer as a PDT drug. We discovered that the 1:1 complex between PCRed and Lu(III) significantly increases the cellular uptake, ROS production and antiproliferative capacity in four cancer cell lines. Our study shows that metal complexation is a useful strategy to potentiate iso-pentaphyrin as a PDT drug.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Screening Assays, Antitumor
  • HeLa Cells
  • Humans
  • Lutetium / chemistry*
  • Metalloporphyrins / chemical synthesis
  • Metalloporphyrins / chemistry
  • Metalloporphyrins / pharmacology*
  • Mice
  • Molecular Structure
  • Photochemotherapy
  • Photosensitizing Agents / chemical synthesis
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / pharmacology*
  • Reactive Oxygen Species / metabolism*
  • Stereoisomerism
  • Zinc / chemistry

Substances

  • Antineoplastic Agents
  • Metalloporphyrins
  • Photosensitizing Agents
  • Reactive Oxygen Species
  • Lutetium
  • Zinc