PHOTODYNAMIC EFFECTS OF NEW SILICON PHTHALOCYANINES - IN-VITRO STUDIES UTILIZING RAT HEPATIC MICROSOMES AND HUMAN ERYTHROCYTE-GHOSTS AS MODEL MEMBRANE SOURCES

Photodynamic therapy (PDT) of cancer is a modality that relies upon th e irradiation of tumors with visible light following selective uptake of a photosensitizer by the tumor tissue. There is considerable emphas is to define new photosensitizers suitable for PDT of cancer. In this study we evaluated six phthalocyanines (Pc) for their photodynamic eff ects utilizing rat hepatic microsomes and human erythrocyte ghosts as model membrane sources. Of the newly synthesized Pc, two showed signif icant destruction of cytochrome P-450 and monooxygenase activities, an d enhancement of lipid peroxidation, when added to microsomal suspensi on followed by irradiation with almost-equal-to 675 nm light. These tw o Pc named SiPc IV (HOSiPcOSi[CH3]2[CH2]3N[CH3]2) and SiPc V (HOSiPc-O Si[CH3]2[CH2]3N[CH3]3+I-) showed dose-dependent photodestruction of cy tochrome P-450 and monooxygenase activities in liver microsomes, and p hotoenhancement of lipid peroxidation, lipid hydroperoxide formation a nd lipid fluorescence in microsomes and erythrocyte ghosts. Compared t o chloroaluminum phthalocyanine tetrasulfonate, SiPc IV and SiPc V pro duced far more pronounced photodynamic effects. Sodium azide, histidin e, and 2,5-dimethylfuran, the quenchers of singlet oxygen, afforded hi ghly significant protection against SiPc IV- and SiPc V-mediated photo dynamic effects. However, to a lesser extent, the quenchers of superox ide anion, hydrogen peroxide and hydroxyl radical also showed some pro tective effects. These results suggest that SiPc IV and SiPc V may be promising photosensitizers for the PDT of cancer.