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Targeting of multidrug-resistant human ovarian carcinoma cells with anti-P-glycoprotein antibody conjugates
Authors:Fowers Kirk D  Kopeček Jindřich
Affiliation:Department of Bioengineering, University of Utah, Salt Lake City, UT 84112, USA.
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.
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