Atorvastatin and clopidogrel interfere with photosensitization in vitro

Photochem Photobiol Sci. 2011 Oct;10(10):1587-92. doi: 10.1039/c0pp00363h. Epub 2011 Jul 12.

Abstract

Photodynamic therapy (PDT) has been used to eliminate undesired cells by using a combination of photosensitizers and light illumination to generate reactive oxygen species. There is great interest in applying PDT to atherosclerosis; preferential destruction of pro-inflammatory macrophages in atheromata might attenuate plaque growth or rupture-prone vulnerability. Here, we report on a previously unknown interaction between cardiovascular drugs that are commonly prescribed for atherosclerosis patients and the cytolytic effects of photodynamic therapy using Cathepsin B activatable photosensitizer L-SR15 on murine macrophage Raw 264.7 cells in culture. Atorvastatin and clopidogrel significantly interfered with in vitro photosensitization effect while aspirin did this to a lesser extent; these drugs did not change the efficiency of cellular uptake of L-SR15 after in vitro photosensitization. A photosensitization interference effect of atorvastatin and clopidogrel was also observed when using a conventional photosensitizer free Ce6 or NCI-H1299 cancer cells. Considering the clinical implications of PDT, our study merits further investigation in clinical settings as well as in animal models.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticholesteremic Agents / pharmacology*
  • Aspirin / pharmacology
  • Atorvastatin
  • Cathepsin B / metabolism
  • Cell Line
  • Clopidogrel
  • Heptanoic Acids / pharmacology*
  • Humans
  • Light
  • Macrophages / drug effects
  • Mice
  • Neoplasms / drug therapy
  • Photochemotherapy
  • Photosensitizing Agents / therapeutic use
  • Photosensitizing Agents / toxicity*
  • Polyethylene Glycols / chemical synthesis
  • Polyethylene Glycols / chemistry
  • Polyethylene Glycols / toxicity*
  • Polylysine / analogs & derivatives*
  • Polylysine / chemical synthesis
  • Polylysine / chemistry
  • Polylysine / toxicity
  • Porphyrins / chemical synthesis
  • Porphyrins / chemistry
  • Porphyrins / toxicity*
  • Pyrroles / pharmacology*
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / pharmacology

Substances

  • Anticholesteremic Agents
  • Heptanoic Acids
  • Photosensitizing Agents
  • Porphyrins
  • Pyrroles
  • Polylysine
  • Polyethylene Glycols
  • Atorvastatin
  • Clopidogrel
  • Cathepsin B
  • Ticlopidine
  • Aspirin