title: Targeting of multidrug-resistant human ovarian carcinoma cells with anti-P-glycoprotein antibody conjugates.
abstract: A monoclonal antibody (mAb) to P-glycoprotein (Pgp), UIC2, is used as a targeting moiety for N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer/drug [(meso chlorin e(6) mono(N-2-aminoethylamide) (Mce(6)) or doxorubicin (DOX)] conjugates to investigate their cytotoxicity towards the Pgp-expressing human ovarian carcinoma cell line A2780/AD. The binding, internalization, and subcellular trafficking of a fluorescein labeled UIC2 targeted HPMA copolymer are studied and show localization to the plasma membrane with limited internalization. The specificity of the UIC2-targeted HPMA copolymer/drug conjugates are confirmed using the sensitive cell line A2780 that does not express Pgp.
authors.affiliation: Department of Bioengineering, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Kirk D
authors.initials: KD
authors.lastname: Fowers
authors.forename: Jindřich
authors.initials: J
authors.lastname: Kopeček
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000737:chemistry / Q000378:metabolism; D000180:Acrylic Resins / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002277:Carcinoma / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000737:chemistry* / Q000494:pharmacology; D004337:Drug Carriers; D019008:Drug Resistance, Neoplasm; D004705:Endocytosis / Q000187:drug effects; D005260:Female; D019793:Fluorescein; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry* / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000473:pathology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000180:Acrylic Resins; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D004337:Drug Carriers; D018796:Immunoconjugates; D004317:Doxorubicin; D019793:Fluorescein