title: Production of the free radicals O2.- and .OH by irradiation of the photosensitizer zinc(II) phthalocyanine.
abstract: Zinc(II) phthalocyanine (ZnPC) is a new photosensitizer currently undergoing phase I and II clinical trials at Lausanne's CHUV hospital for the photodynamic therapy (PDT) of early cancer in the upper aerodigestive tract. Activated oxygen species other than singlet oxygen produced during the photosensitization of ZnPC in liposomes have been examined by electron paramagnetic resonance (EPR) spin trapping and by the cytochrome c reduction method. Visible light irradiation of ZnPC associated with liposomes in the presence of the spin trap 5,5-dimethyl-1-pyrroline-1-oxide (DMPO) gives an EPR spectrum characteristic of the DMPO-hydroperoxyl radical spin adduct (DMPO-.OOH). Superoxide anion attains a level of 1 microM min-1 20 min after the start of irradiation as determined by the superoxide dismutase (SOD)-inhibitable reduction of cytochrome c. The yield of O2.- is strongly enhanced by physiological electron donors. An EPR spectrum characteristic of the DMPO-hydroxyl radical spin adduct (DMPO-.OH) is also observed. The addition of dimethyl sulphoxide or ethanol produces additional hyperfine splittings due to the respective hydroxyalkyl radical products, indicating the presence of free .OH. DMPO-.OH is significantly inhibited by desferrioxamine or catalase. Conversely, this adduct is enhanced by hydrogen peroxide. These data demonstrate the ability of ZnPC in liposomes to photoreact effectively by an electron transfer mechanism. Such type I processes may add to the effects of singlet oxygen in ZnPC-mediated PDT.
authors.affiliation: Institut du Génie de l'Environnement, Ecole Polytechnique Fédérale de Lausanne, DGR-LPAS, Lausanne, Switzerland. hadjur@dgr.epfl.ch
authors.forename: C
authors.initials: C
authors.lastname: Hadjur
authors.forename: G
authors.initials: G
authors.lastname: Wagnières
authors.forename: F
authors.initials: F
authors.lastname: Ihringer
authors.forename: P
authors.initials: P
authors.lastname: Monnier
authors.forename: H
authors.initials: H
authors.lastname: van den Bergh
mesh_terms: D003497:Cyclic N-Oxides / Q000378:metabolism; D003574:Cytochrome c Group / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D017665:Hydroxyl Radical / Q000378:metabolism*; D007211:Indoles / Q000528:radiation effects*; D054833:Isoindoles; D008027:Light; D008081:Liposomes; D009942:Organometallic Compounds / Q000528:radiation effects*; D017319:Photosensitizing Agents / Q000528:radiation effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013054:Spectrophotometry, Atomic; D013481:Superoxides / Q000378:metabolism*; D017967:Zinc Compounds
chemical_list: D003497:Cyclic N-Oxides; D003574:Cytochrome c Group; D007211:Indoles; D054833:Isoindoles; D008081:Liposomes; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species; D017967:Zinc Compounds; D013481:Superoxides; C052159:Zn(II)-phthalocyanine; D017665:Hydroxyl Radical; C069977:2,2-dimethyl-5-hydroxy-1-pyrrolidinyloxy