Specific targeting and toxicity of sulphonated aluminium phthalocyanine photosensitised liposomes directed to cells by monoclonal antibody in vitro.
A partially purified fraction of the water soluble photosensitive dye sulphonated aluminium phthalocyanine (AlSPc) was encapsulated in liposomes which were then linked to a targeting monoclonal antibody 791T/36 using a heterobifunctional linking agent. The photocytotoxic effects of the liposomes were determined on two cell lines bearing an antigen with which the targeting antibody binds: 791T, an osteosarcoma and C170, a colorectal carcinoma; and a control cell line not bearing the antigen; DW-BCL, an Epstein-Barr virus immortalised B-cell line. Antibody dependent cytotoxicity was observed in 791T and C170 cells and was proportional to the number of antigens on the cells, the AlSPc concentration and the time of exposure to activating red light. No significant toxicity was seen using untargeted liposomes, control cells or free AlSPc fraction under similar conditions. Targeted cells and controls kept in the dark also showed no significant toxicity. A possible mechanism of action is postulated and simple adaptations which demonstrate the versatility of the model are discussed. Some suggestions as to the clinical situations to which this system might be applied in the form of photodynamic therapy (PDT) are made.
Morgan
J
J
Department of Haematology, University College, Middlesex School of Medicine, London, UK.
Gray
A G
AG
Huehns
E R
ER
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D004337:Drug Carriers; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000627:therapeutic use; D008081:Liposomes; D009942:Organometallic Compounds / Q000008:administration & dosage* / Q000627:therapeutic use; D010778:Photochemotherapy; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D004337:Drug Carriers; D007211:Indoles; D008081:Liposomes; D009942:Organometallic Compounds; C048577:aluminum tetrasulfophthalocyanine