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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.

SUBMITTER: Larson N 

PROVIDER: S-EPMC4262670 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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In vitro synergistic action of geldanamycin- and docetaxel-containing HPMA copolymer-RGDfK conjugates against ovarian cancer.

Larson Nate N   Roberts Sarah S   Ray Abhijit A   Buckway Brandon B   Cheney Darwin L DL   Ghandehari Hamidreza H  

Macromolecular bioscience 20140904 12


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 a  ...[more]

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