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 incorporated into immunoliposomes coated with a monoclonal antibody (T-43) directed against the T-24 bladder tumor cell line. The efficacy of this system was studied in vitro using the human bladder tumor cell line MGH-U1. Uptake and localization were determined by the fluorescence of the immunoliposome markers within biochemically resolved subcellular components. The results demonstrate localization of the immunoliposome markers within the lysosomes of the tumor cells. Specific monoclonal antibody enhancement of the immunoliposomes uptake by MGH-U1 cells was demonstrated by the use of soluble T-43 monoclonal antibody as a competitive inhibitor. Pheophorbide-a-loaded immunoliposomes were shown to 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 subsequent 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 potentially valuable approach to photodynamic therapeutics.
Bergstrom
L C
LC
Fiber Optics Materials Research Program, Rutgers University, Piscataway, NJ 08854.
Vucenik
I
I
Hagen
I K
IK
Chernomorsky
S A
SA
Poretz
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RD
D000911:Antibodies, Monoclonal; D002295:Carcinoma, Transitional Cell; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002734:Chlorophyll / Q000031:analogs & derivatives* / Q000633:toxicity; D003624:Darkness; D004337:Drug Carriers; D006801:Humans; D008027:Light; D008081:Liposomes; D008247:Lysosomes / Q000187:drug effects*; D011838:Radiation-Sensitizing Agents / Q000633:toxicity*; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms
D000911:Antibodies, Monoclonal; D004337:Drug Carriers; D008081:Liposomes; D011838:Radiation-Sensitizing Agents; D002734:Chlorophyll; C032623:pheophorbide a