title: Selective photosensitization of mitochondria in HeLa cells by cationic Zn (II) phthalocyanines with lipophilic side-chains.
abstract: In order to optimize the photosensitization of mitochondria, we prepared the new cationic zinc (II) phthalocyanines with lipophilic side-chains (2,9,16,23-tetrakis (trimethylammonio) zinc (II) phthalocyanine tetramethylsulphate (ZnPcA1) and 2,9,16,23-tetrakis(hexyldimethylammonio) zinc (II) phthalocyanine tetramethylsulphate (ZnPcA6)) and compared them with the known cationic lipophilic sensitizers 2,9,16,23-tetrakis[2-(trimethylammonio) ethoxy]zinc (II) phthalocyanine tetraiodide (ZnPcE1) and 2,9,16,23-tetrakis[2-(hexyldimethylammonio) ethoxy] zinc (II) phthalocyanine tetrabromide (ZnPcE6) and the anionic hydrophilic sulphonated sensitizer ZnPcS. The absorption and fluorescence spectra, fluorescence quantum yields, partition coefficients Po/w between octanol and water, dimerization of ZnPcA1 in water and photosensitized generation of singlet oxygen were examined. Moreover, the phototoxic and cytotoxic effects of the phthalocyanines on HeLa cells, their photodynamic action on the proliferation rate and the influence of irradiation on the respiratory activity were studied and compared with electron and fluorescence microscopic observations of the ultrastructure of incubated and irradiated HeLa cells. From our experiments, we conclude that cationic lipophilic sensitizers, such as ZnPcA6, etc., specifically accumulate in the inner mitochondrial membranes. Therefore they can be used for the selective photosensitization of mitochondria. On irradiation of the incubated HeLa cells, the cristae are affected and finally completely destroyed. The respiration stops and the energy metabolism breaks down. Our experiments indicate that the phototoxic efficacy of the sensitizers decreases in the following order: ZnPcA6 > ZnPcA1 > ZnPcE6 > ZnPcE1 > ZnPcS. The cationic lipophilic ZnPcA6 has the strongest phototoxic activity. It acts on incubation at very low sensitizer concentrations and short irradiation periods. The dark toxicity is completely negligible. The phototoxic activity follows the type II mechanism.
authors.affiliation: Institut für Physikalische Chemie, Universität Freiburg, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Dummin
authors.forename: T
authors.initials: T
authors.lastname: Cernay
authors.forename: H W
authors.initials: HW
authors.lastname: Zimmermann
mesh_terms: D006367:HeLa Cells; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D054833:Isoindoles; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000187:drug effects*; D009942:Organometallic Compounds / Q000494:pharmacology*; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology*; D013050:Spectrometry, Fluorescence; D013054:Spectrophotometry, Atomic; D017967:Zinc Compounds
chemical_list: D007211:Indoles; D054833:Isoindoles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D017967:Zinc Compounds; C052159:Zn(II)-phthalocyanine