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 the irradiation of tumors with visible light following selective uptake of a photosensitizer by the tumor tissue. There is considerable emphasis to define new photosensitizers suitable for PDT of cancer. In this study we evaluated six phthalocyanines (Pc) for their photodynamic effects utilizing rat hepatic microsomes and human erythrocyte ghosts as model membrane sources. Of the newly synthesized Pc, two showed significant destruction of cytochrome P-450 and monooxygenase activities, and enhancement of lipid peroxidation, when added to microsomal suspension followed by irradiation with approximately 675 nm light. These two Pc named SiPc IV (HOSiPcOSi[CH3]2[CH2]3N[CH3]2) and SiPc V (HOSiPc-OSi[CH3]2[CH2]3N[CH3]3+I-) showed dose-dependent photodestruction of cytochrome P-450 and monooxygenase activities in liver microsomes, and photoenhancement of lipid peroxidation, lipid hydroperoxide formation and lipid fluorescence in microsomes and erythrocyte ghosts. Compared to chloroaluminum phthalocyanine tetrasulfonate, SiPc IV and SiPc V produced far more pronounced photodynamic effects. Sodium azide, histidine, and 2,5-dimethylfuran, the quenchers of singlet oxygen, afforded highly significant protection against SiPc IV- and SiPc V-mediated photodynamic effects. However, to a lesser extent, the quenchers of superoxide anion, hydrogen peroxide and hydroxyl radical also showed some protective effects. These results suggest that SiPc IV and SiPc V may be promising photosensitizers for the PDT of cancer.
Zaidi
S I
SI
Department of Dermatology, Skin Diseases Research Center, University Hospitals of Cleveland, Case Western Reserve University, OH.
Agarwal
R
R
Eichler
G
G
Rihter
B D
BD
Kenney
M E
ME
Mukhtar
H
H
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004910:Erythrocyte Membrane / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D054833:Isoindoles; D008027:Light; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008563:Membrane Lipids / Q000097:blood; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D010778:Photochemotherapy; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012825:Silicon / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D007211:Indoles; D054833:Isoindoles; D008563:Membrane Lipids; D011838:Radiation-Sensitizing Agents; D003577:Cytochrome P-450 Enzyme System; C013647:phthalocyanine; D012825:Silicon