IN-VITRO PHOTOCYTOTOXICITY OF LYSOSOMOTROPIC IMMUNOLIPOSOMES CONTAINING PHEOPHORBIDE A WITH HUMAN BLADDER-CARCINOMA CELLS

Pheophorbide a is a photocytotoxic agent. To develop a tissue-specific , intracellularly targeted photoactive system, pheophorbide a was inco rporated into immunoliposomes coated with a monoclonal antibody (T-43) directed against the T-24 bladder tumor cell line. The efficacy of th is system was studied in vitro using the human bladder tumor cell line MGH-U1. Uptake and localization were determined by the fluorescence o f the immunoliposome markers within biochemically resolved subcellular components. The results demonstrate localization of the immunoliposom e markers within the lysosomes of the tumor cells. Specific monoclonal antibody enhancement of the immunoliposomes uptake by MGH-U1 cells wa s demonstrated by the use of soluble T-43 monoclonal antibody as a com petitive inhibitor. Pheophorbide-a-loaded immunoliposomes were shown t o be photocytotoxic towards MGH-U1 cells at concentrations equivalent to photosensitizer at 500 ng ml(-1) Treated cells, when protected from light, showed no cytotoxicity. These results demonstrate that uptake of pheophorbide-a-containing immunoliposomes by target cells and subse quent delivery to the lysosomes cause photoactivated killing of tumor cells. The utilization of immunoliposomes for intracellular lysosomal targeting of photoactive drugs to tumor cells constitutes a potentiall y valuable approach to photodynamic therapeutics.