Synergistic effects of cisplatin chemotherapy and gold nanorod-mediated hyperthermia on ovarian cancer cells and tumors

Abstract

Aim: The synergistic effects of gold nanorod (GNR)-mediated mild hyperthermia (MHT; 42–43°C) and cisplatin (CP) activity was evaluated against chemoresistant SKOV3 cells in vitro and with a tumor xenograft model. Materials & methods: In vitro studies were performed using CP at cytostatic concentrations (5 µM) and polyethylene glycol-stabilized GNRs, using near-infrared laser excitation for MHT. Results: The amount of polyethylene glycol-GNRs used for environmental MHT was 1 µg/ml, several times lower than the loadings used in tumor tissue ablation. GNR-mediated MHT increased CP-mediated cytotoxicity by 80%, relative to the projected additive effect, and flow cytometry analysis suggested MHT also enhanced CP-induced apoptosis. In a pilot in vivo study, systemically administered polyethylene glycol-GNRs generated sufficient levels of MHT to enhance CP-induced reductions in tumor volume, despite their heterogeneous distribution in tumor tissue. Conclusion: These studies imply that effective chemotherapies can be developed in combination with low loadings of nanoparticles for localized MHT. Original submitted 6 July 2013; Revised submitted 20 October 2013