title: The characterisation of three substituted zinc phthalocyanines of differing charge for use in photodynamic therapy. A comparative study of their aggregation and photosensitising ability in relation to mTHPC and polyhaematoporphyrin.
abstract: Three substituted zinc (II) phthalocyanines (one anionic, one cationic and one hydrophobic) have been compared to two clinically used photosensitisers, 5,10,15,20-tetra (m-hydroxyphenyl) chlorin (mTHPC) and polyhaematoporphyrin (PHP), as potential agents for photodynamic therapy (PDT). Oxygen-consumption experiments, performed to follow the photo-oxidation of tryptophan, histidine and bovine serum albumin (BSA), suggest that the anionic phthalocyanine is the most efficient photosensitiser. The efficacy of BSA oxidation is much greater than that of tryptophan or histidine, which is partly due to monomerisation of the sensitisers upon binding to BSA. Spectra recorded in aqueous solution reveal that all five compounds are highly aggregated, but monomerisation is induced upon the addition of BSA or methanol. Using a range of methanol-buffer solutions, the aggregation state has been directly related to the efficacy of tryptophan photo-oxidation with maximal rates of oxidation achieved when the sensitiser is monomeric. Using erythrocytes as a simple membrane model, the efficacy of each sensitiser exhibits a different trend from that predicted by oxygen-consumption experiments. The anionic phthalocyanine is the least effective at photohaemolysis, whereas the cationic and hydrophobic phthalocyanines have improved activity over PHP and mTHPC.
authors.affiliation: Centre for Photobiology and Photodynamic Therapy, University of Leeds, UK. bmbdjb@bmb.leeds.ac.uk
authors.forename: D J
authors.initials: DJ
authors.lastname: Ball
authors.forename: S R
authors.initials: SR
authors.lastname: Wood
authors.forename: D I
authors.initials: DI
authors.lastname: Vernon
authors.forename: J
authors.initials: J
authors.lastname: Griffiths
authors.forename: T M
authors.initials: TM
authors.lastname: Dubbelman
authors.forename: S B
authors.initials: SB
authors.lastname: Brown
mesh_terms: D000818:Animals; D002417:Cattle; D004912:Erythrocytes / Q000187:drug effects*; D006639:Histidine; D006801:Humans; D007211:Indoles / Q000737:chemistry* / Q000494:pharmacology; D054833:Isoindoles; D000432:Methanol; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry* / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000737:chemistry* / Q000494:pharmacology; D010084:Oxidation-Reduction; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000494:pharmacology; D011166:Porphyrins / Q000737:chemistry* / Q000494:pharmacology; D012710:Serum Albumin, Bovine / Q000187:drug effects / Q000378:metabolism; D014364:Tryptophan; D017967:Zinc Compounds
chemical_list: D007211:Indoles; D054833:Isoindoles; D009942:Organometallic Compounds; D009943:Organophosphorus Compounds; D017319:Photosensitizing Agents; D011166:Porphyrins; D017967:Zinc Compounds; C115907:polyhaematoporphyrin; C014850:tetramethylolphosphonium chloride; C052159:Zn(II)-phthalocyanine; D012710:Serum Albumin, Bovine; D006639:Histidine; D014364:Tryptophan; D000432:Methanol