Targetability and intracellular delivery of anti-BCG antibody-modified, pH-sensitive fusogenic immunoliposomes to tumor cells.
We prepared tumor-specific immunoliposomes by coupling anti-BCG monoclonal antibodies to pH-sensitive fusogenic liposomes modified with succinylated polyglycidol (sucPG), in order to obtain efficient binding to, and endocytotic internalization into, the tumor cells. Mouse colon carcinoma 26 cells, which are known to share a common antigen with BCG, were used in in vitro experiments. BCG-sucPG immunoliposomes showed fusion ability under acidic conditions. Fluorescence microscopic observation indicated that BCG-sucPG immunoliposomes bound to colon 26 tumor cells and induced receptor-mediated endocytosis at 37 degrees C. Fusion assay by resonance energy transfer using N-(7-nitro-2-1,3-benzoxadiazol-4-yl) diacyl phosphatidylethanolamine and N-(lissamine rhodamine B sulfonyl) diacyl phosphatidylethanolamine suggested that fusion between BCG-sucPG immunoliposomes and endosomal and/or lysozomal membrane did occur. These results imply that the BCG-sucPG immunoliposomes transfer their content into the cytoplasm by fusing with the endosomal and/or lysozomal membrane after recognition of target cells and subsequent internalization into the cells by endocytosis.
Mizoue
Toshiro
T
The Fourth Department of Internal Medicine, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan.
Horibe
Toshiya
T
Maruyama
Kazuo
K
Takizawa
Tomoko
T
Iwatsuru
Motoharu
M
Kono
Kenji
K
Yanagie
Hironobu
H
Moriyasu
Fuminori
F
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage*; D000907:Antibodies, Bacterial / Q000008:administration & dosage*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002417:Cattle; D016503:Drug Delivery Systems / Q000379:methods*; D006863:Hydrogen-Ion Concentration; D000922:Immunotoxins / Q000008:administration & dosage / Q000493:pharmacokinetics; D007424:Intracellular Fluid / Q000187:drug effects* / Q000378:metabolism; D008081:Liposomes; D051379:Mice; D009163:Mycobacterium bovis / Q000276:immunology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D000888:Antibodies, Anti-Idiotypic; D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D008081:Liposomes