In vivo targeting of OV-TL 3 immunoliposomes to ascitic ovarian carcinoma cells (OVCAR-3) in athymic nude mice.
Specific binding of immunoliposomes to target tumor cells was investigated in a xenograft model (athymic nude mice) of i.p. growing human ovarian carcinoma (OVCAR-3). For the first time, quantitative evidence is presented that attachment of a tumor-specific antibody (OV-TL 3) dramatically enhances the association of liposomes with i.p. growing OVCAR-3 cells. The OV-TL 3-mediated binding of liposomes to the OVCAR-3 cells was rapid; 30 min after i.p. injection approximately 70% of the injected dose of OV-TL 3 immunoliposomes was associated with the OVCAR-3 cells while for unconjugated liposomes a value of only approximately 3% was obtained. At 2 h after injection, a maximal binding level of 84% was achieved in case of the OV-TL 3 immunoliposomes whereas the binding level of unconjugated liposomes was still about 3%. Twenty-four h after injection about 83% of the injected dose OV-TL 3 immunoliposomes still was associated with the OVCAR-3 cells, compared to about 10% of the injected dose of unconjugated liposomes. Accordingly, unconjugated liposomes disappeared from the peritoneal cavity much faster than the OV-TL 3 immunoliposomes. By comparison with immunoliposomes bearing irrelevant antibody, the specificity of the binding of the OV-TL 3 immunoliposomes to the OVCAR-3 cells was demonstrated. In addition, it was observed that the sustained high OV-TL 3 immunoliposome levels found in the peritoneal cavity are the result of both reduced particle clearance from the peritoneal cavity and the tenacious binding of the immunoliposomes to the tumor cells. Finally, data are presented showing that the degree of binding of OV-TL 3 immunoliposomes to OVCAR-3 cells in vitro and in vivo correlates positively with the antibody (Fab') density on the liposomes.
Nässander
U K
UK
Department of Pharmaceutics, Faculty of Pharmacy, University of Utrecht, The Netherlands.
Steerenberg
P A
PA
Poppe
H
H
Storm
G
G
Poels
L G
LG
De Jong
W H
WH
Crommelin
D J
DJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000378:metabolism; D002250:Carbon Radioisotopes; D002460:Cell Line; D002784:Cholesterol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D004337:Drug Carriers; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage* / Q000378:metabolism; D007700:Kinetics; D008081:Liposomes; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000276:immunology / Q000378:metabolism*; D013395:Sucrose / Q000008:administration & dosage / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D014316:Tritium
D000911:Antibodies, Monoclonal; D002250:Carbon Radioisotopes; D004337:Drug Carriers; D007140:Immunoglobulin Fab Fragments; D008081:Liposomes; D014316:Tritium; D013395:Sucrose; C023511:cholesteryl oleyl ether; D002784:Cholesterol