THE CHARACTERIZATION OF 3 SUBSTITUTED ZINC PHTHALOCYANINES OF DIFFERING CHARGE FOR USE IN PHOTODYNAMIC THERAPY - A COMPARATIVE-STUDY OF THEIR AGGREGATION AND PHOTOSENSITIZING ABILITY IN RELATION TO MTHPC AND POLYHEMATOPORPHYRIN

Three substituted zinc (II) phthalocyanines tone anionic, one cationic and one hydrophobic) have been compared to two clinically used photos ensitisers, 5,10,15,20-tetra(m-hydroxyphenyl) chlorin (mTHPC) and poly haematoporphyrin (PHP), as potential agents for photodynamic therapy ( PDT). Oxygen-consumption experiments, performed to follow the photo-ox idation of tryptophan, histidine and bovine serum albumin (BSA), sugge st that the anionic phthalocyanine is the most efficient photosensitis er. The efficacy of BSA oxidation is much greater than that of tryptop han or histidine, which is partly due to monomerisation of the sensiti sers upon binding to BSA. Spectra recorded in aqueous solution reveal that all five compounds are highly aggregated, but monomerisation is i nduced 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 oxida tion achieved when the sensitiser is monomeric. Using erythrocytes as a simple membrane model, the efficacy of each sensitiser exhibits a di fferent trend from that predicted by oxygen-consumption experiments. T he anionic phthalocyanine is the least effective at photohaemolysis, w hereas the cationic and hydrophobic phthalocyanines have improved acti vity over PHP and mTHPC. (C) 1998 Elsevier Science S.A. All rights res erved.