Faculty Collaboration Database

A molecularly targeted theranostic probe for ovarian cancer. Mol Cancer Ther 2010 Apr;9(4):1028-38

Date

04/08/2010

Pubmed ID

20371708

Pubmed Central ID

PMC4134931

DOI

10.1158/1535-7163.MCT-09-0829

Scopus ID

2-s2.0-77950803620 (requires institutional sign-in at Scopus site)   77 Citations

Abstract

Overexpression of the human epidermal growth factor receptor (HER) family has been implicated in ovarian cancer because of its participation in signaling pathway regulating cellular proliferation, differentiation, motility, and survival. Currently, effective diagnostic and therapeutic schemes are lacking for treating ovarian cancer, and consequently ovarian cancer has a high mortality rate. Although HER2 receptor expression does not usually affect the survival rates of ovarian cancer to the same extent as in breast cancer, it can be used as a docking site for directed nanotherapies in cases with de novo or acquired chemotherapy resistance. In this study, we have exploited a novel gold nanoshell-based complex (nanocomplex) for targeting, dual modal imaging, and photothermal therapy of HER2-overexpressing and drug-resistant ovarian cancer OVCAR3 cells in vitro. The nanocomplexes are engineered to simultaneously provide contrast as fluorescence optical imaging probe and a magnetic resonance imaging agent. Immunofluorescence staining and magnetic resonance imaging successfully show that nanocomplex-anti-HER2 conjugates specifically bind to OVCAR3 cells as opposed to the control, MDA-MB-231 cells, which have low HER2 expression. In addition, nanocomplexes targeted to OVCAR3 cells, when irradiated with near-IR laser, result in selective destruction of cancer cells through photothermal ablation. We also show that near-IR light therapy and the nanocomplexes by themselves are noncytotoxic in vitro. To the best of our knowledge, this is the first successful integration of dual modal bioimaging with photothermal cancer therapy for treatment of ovarian cancer. Based on their efficacy in vitro, these nanocomplexes are highly promising for image-guided photothermal therapy of ovarian cancer, as well as other HER2-overexpressing cancers. Mol Cancer Ther; 9(4); 1028-38. (c)2010 AACR.

Author List

Chen W, Bardhan R, Bartels M, Perez-Torres C, Pautler RG, Halas NJ, Joshi A

Author

Amit Joshi PhD Professor in the Biomedical Engineering department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Ablation Techniques
Cell Death
Cell Line, Tumor
Contrast Media
Female
Humans
Magnetic Resonance Imaging
Microscopy, Fluorescence
Molecular Probes
Nanoshells
Ovarian Neoplasms
Receptor, ErbB-2
Temperature