A nonviral carrier for targeted gene delivery to tumor cells.
In this study, we developed a nonviral, cationic, targeted DNA-carrier system by coupling SAINT/DOPE lipids to monoclonal antibodies. The two monoclonal antibodies used were both tumor specific, that is, MOC31 recognizes the epithelial glycoprotein EGP-2 present in carcinomas and Herceptin recognizes the HER-2/neu protein in breast and ovarian cancers. Coupling was performed under nonreducing conditions by covalent attachment. The coupling procedure appeared to be reproducible and the binding capacity of the antibody was not affected by linking them to the cationic lipid. Binding and transfection efficiency was assayed with target cells and nontarget cells. SAINT/DOPE lipoplexes as such appeared to be an effective transfection reagent for various cell lines. After coupling SAINT/DOPE to the monoclonal antibodies or F(ab)2 fragments, it was shown that the targeted MoAb-SAINT/DOPE lipoplexes preferably bound to target cells, compared to binding to the nontarget cells, especially for the Herceptin-SAINT/DOPE lipoplexes. More importantly, transfection of the target cells could also be improved with these targeted lipoplexes. In conclusion, we have shown that by using monoclonal antibody-coupled SAINT/DOPE lipoplexes cells targeted gene delivery can be achieved, and also a higher number of transfected target cells was seen.
van Zanten
Jacoba
J
Department of PLG/Medical Biology, Academic Hospital Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands. J.van.Zanten@med.rug.nl
Doornbos-Van der Meer
Berber
B
Audouy
Sandrine
S
Kok
Robbert Jan
RJ
de Leij
Lou
L
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000378:metabolism; D061067:Antibodies, Monoclonal, Humanized; D002412:Cations / Q000378:metabolism; D045744:Cell Line, Tumor; D004247:DNA / Q000008:administration & dosage / Q000378:metabolism; D018390:Gene Targeting; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism; D050356:Lipid Metabolism; D008081:Liposomes / Q000378:metabolism; D008545:Melanoma / Q000628:therapy; D051379:Mice; D009369:Neoplasms / Q000628:therapy*; D010714:Phosphatidylethanolamines / Q000378:metabolism; D010957:Plasmids; D012878:Skin Neoplasms / Q000628:therapy; D014162:Transfection / Q000379:methods*; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D002412:Cations; D007140:Immunoglobulin Fab Fragments; D008081:Liposomes; D010714:Phosphatidylethanolamines; C094877:dioleoyl phosphatidylethanolamine; D004247:DNA; D000068878:Trastuzumab