Liposome-bound Zn(II)-phthalocyanine. Mechanisms for cellular uptake and photosensitization

In the present study, cellular uptake of a liposomal formulation of ZnPc(CG P 55847) has been studied in human cervix carcinoma cells of the line NHIK 3025. The cellular uptake of ZnPc is found to be completed after 4-8 h of i ncubation. The maximum level of ZnPc in the cells after incubation with I m u g/ml ZnPc in E2a medium containing 3% serum is 60 ng/mg protein. The cell ular uptake is attenuated by the presence of serum and at low temperature o f the incubation medium, but the activation energy (30 kJ/mol) and fluoresc ence microscopic analysis of cells incubated with ZnPc at 0 degrees C indic ate that ZnPc is taken up into cells by a diffusion-mediated pathway. Measu rements of subcellular marker enzymes have been performed immediately after light exposure of ZnPc-treated cells. The mitochondrial marker enzyme (cyt ochrome c oxidase) and the marker enzyme for the Golgi apparatus (UDP galac tosyl transferase), but not those for lysosomes (beta-N-acetyl-D-glucosamin idase) and endoplasmic reticulum (NADPH cytochrome c reductase), are inacti vated upon photodynamic treatment. These results indicate that ZnPc is main ly located in the Golgi apparatus and the mitochondria of NHIK 3025 cells. In contrast, photoactivated Photofrin is found to reduce the activity of UD P galactosyl transferase, but not that of NADPH cytochrome c reductase. The tetraphenylporphine TPPS2a and light reduce the activity of NADPH cytochro me c reductase, without influencing the activity of UDP galactosyl transfer ase. TPPS4 and light do not attenuate the activities of UDP galactosyl tran sferase and NADPH cytochrome c reductase. (C) 1998 Elsevier Science S.A. Al l rights reserved.