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


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.


CONCLUSIONS
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.
Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, IN 47907-2084, USA.
Jonathan G
JG
Mehtala
Sandra
S
Torregrosa-Allen
Bennett D
BD
Elzey
Mansik
M
Jeon
Chulhong
C
Kim
Alexander
A
Wei
D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D004357:Drug Synergism; D005260:Female; D006046:Gold / Q000008:administration & dosage*; D006801:Humans; D006979:Hyperthermia, Induced; D043942:Nanotubes / Q000009:adverse effects*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology
D006046:Gold; D002945:Cisplatin
apoptosis; cisplatin; gold nanorods; hyperthermia; ovarian cancer; synergistic effects