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.
Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / chemistry
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
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Acrylic Resins / chemistry*
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Acrylic Resins / metabolism
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Acrylic Resins / pharmacology
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Antibodies, Monoclonal / chemistry*
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Antibodies, Monoclonal / pharmacology
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / pharmacology
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Carcinoma / drug therapy
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Carcinoma / pathology
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Cell Line, Tumor / drug effects
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Cell Membrane / drug effects*
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Cell Membrane / metabolism
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Cell Survival / drug effects
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Doxorubicin / chemistry*
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Doxorubicin / pharmacology
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Drug Carriers
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Drug Resistance, Neoplasm
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Endocytosis / drug effects
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Female
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Fluorescein
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Humans
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Immunoconjugates / chemistry*
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Immunoconjugates / pharmacology
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Ovarian Neoplasms / drug therapy
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Ovarian Neoplasms / pathology
Substances
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Acrylic Resins
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Antibodies, Monoclonal
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Antineoplastic Agents
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Drug Carriers
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Immunoconjugates
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Doxorubicin
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Fluorescein