title: In vitro synergistic action of geldanamycin- and docetaxel-containing HPMA copolymer-RGDfK conjugates against ovarian cancer.
abstract: HPMA copolymer-RGDfK (HPMA-RGDfK) conjugates bearing either aminohexylgeldanamycin (AHGDM) or docetaxel (DOC) were synthesized and characterized. In vitro stability and binding were evaluated. Cytotoxicity toward ovarian cancer cells was evaluated and the ability of the conjugates to induce cell death was assessed by combination index analysis. Conjugates bearing AHGDM were more stable and exhibited slower drug release than those bearing DOC. Both conjugates demonstrated the ability to bind to avb3 integrins. In combination, HPMA-RGDfK conjugates demonstrated marked synergism as compared to their non-targeted counterparts and free drug controls. HPMA-RGDfK conjugates bearing AHGDM and DOC induce synergistic cytotoxicity in vitro, suggesting their potential as a promising combination therapy.
authors.affiliation: TheraTarget, Inc., 615 Arapeen Dr., Suite 302-Y, Salt Lake City, UT, 84108, USA; Department of Pharmaceutics and Pharmaceutical Chemistry, Center for Nanomedicine, Nano Institute of Utah, Salt Lake City, UT, 84112, USA.
authors.forename: Nate
authors.initials: N
authors.lastname: Larson
authors.forename: Sarah
authors.initials: S
authors.lastname: Roberts
authors.forename: Abhijit
authors.initials: A
authors.lastname: Ray
authors.forename: Brandon
authors.initials: B
authors.lastname: Buckway
authors.forename: Darwin L
authors.initials: DL
authors.lastname: Cheney
authors.forename: Hamidreza
authors.initials: H
authors.lastname: Ghandehari
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D016227:Benzoquinones / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D000077143:Docetaxel; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors; D047029:Lactams, Macrocyclic / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D008689:Methacrylates / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D009842:Oligopeptides / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D043823:Taxoids / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000903:Antibiotics, Antineoplastic; D016227:Benzoquinones; D039302:Integrin alphaVbeta3; D047029:Lactams, Macrocyclic; D008689:Methacrylates; D009842:Oligopeptides; D043823:Taxoids; D000077143:Docetaxel; C047981:arginyl-glycyl-aspartic acid; C032802:hydroxypropyl methacrylate; C001277:geldanamycin
keywords: docetaxel; geldanamycin; ovarian cancer; targeted drug delivery