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: Nate Larson, Sarah Roberts, Abhijit Ray, Brandon Buckway, Darwin L Cheney, Hamidreza Ghandehari
• Journal: Macromolecular bioscience (Macromol Biosci) Vol. 14 Issue 12 Pg. 1735-47 (Dec 2014) ISSN: 1616-5195 [Electronic] Germany
• PMID: 25185891 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Antibiotics, Antineoplastic
• Benzoquinones
• Integrin alphaVbeta3
• Lactams, Macrocyclic
• Methacrylates
• Oligopeptides
• Taxoids
• Docetaxel
• arginyl-glycyl-aspartic acid
• hydroxypropyl methacrylate
• geldanamycin

Topics

• Antibiotics, Antineoplastic (chemistry, pharmacokinetics, pharmacology)
• Benzoquinones (chemistry, pharmacokinetics, pharmacology)
• Cell Death (drug effects)
• Cell Line, Tumor
• Docetaxel
• Drug Screening Assays, Antitumor
• Female
• Humans
• Integrin alphaVbeta3 (antagonists & inhibitors)
• Lactams, Macrocyclic (chemistry, pharmacokinetics, pharmacology)
• Methacrylates (chemistry, pharmacokinetics, pharmacology)
• Oligopeptides (chemistry, pharmacokinetics, pharmacology)
• Ovarian Neoplasms (drug therapy, metabolism, pathology)
• Taxoids (chemistry, pharmacokinetics, pharmacology)