title: Atorvastatin and clopidogrel interfere with photosensitization in vitro.
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.
authors: Molecular Imaging and Neurovascular Research (MINER) Laboratory, Department of Neurology, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, 814 Siksa-dong, Goyang, Korea.
authors: Dong Kun
authors: DK
authors: Lee
authors: Yongdoo
authors: Y
authors: Choi
authors: Soo-Min
authors: SM
authors: Shon
authors: Dawid
authors: D
authors: Schellingerhout
authors: Jin Eok
authors: JE
authors: Park
authors: Dong-Eog
authors: DE
authors: Kim
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology; D000069059:Atorvastatin; D002401:Cathepsin B / Q000378:metabolism; D002460:Cell Line; D000077144:Clopidogrel; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D008027:Light; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use / Q000633:toxicity*; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity*; D011107:Polylysine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D011166:Porphyrins / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity*; D011758:Pyrroles / Q000494:pharmacology*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D017319:Photosensitizing Agents; D011166:Porphyrins; D011758:Pyrroles; D011107:Polylysine; D011092:Polyethylene Glycols; D000069059:Atorvastatin; D000077144:Clopidogrel; D002401:Cathepsin B; D013988:Ticlopidine; D001241:Aspirin