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Surface-enhanced Resonance Raman Scattering Nanoprobe Ratiometry for Detecting Microscopic Ovarian Cancer via Folate Receptor Targeting
Published on: March 25, 2019
A molecularly targeted theranostic probe for ovarian cancer
Wenxue Chen1, Rizia Bardhan, Marc Bartels
1Baylor College of Medicine, BCM 360, 1 Baylor Plaza, Houston, TX 77030, USA.
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.
Insights
This study introduces a novel gold nanoshell complex for dual imaging and photothermal therapy of drug-resistant ovarian cancer. The nanocomplex targets HER2-overexpressing cells, enabling precise imaging and selective cancer cell destruction via near-infrared laser irradiation.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Overexpression of the human epidermal growth factor receptor (HER) family is linked to ovarian cancer progression.
- Ovarian cancer has a high mortality rate due to a lack of effective diagnostic and therapeutic strategies.
- HER2 receptor expression offers a potential target for nanotherapies in drug-resistant ovarian cancer.
Purpose of the Study:
- To develop and evaluate a novel gold nanoshell-based nanocomplex for targeting, dual modal imaging, and photothermal therapy of HER2-overexpressing, drug-resistant ovarian cancer cells (OVCAR3) in vitro.
- To assess the specificity of the nanocomplex for HER2-overexpressing cells.
- To investigate the efficacy of photothermal therapy using the nanocomplex and near-infrared laser irradiation.
Main Methods:
- Engineered gold nanoshell-based nanocomplexes capable of fluorescence optical imaging and magnetic resonance imaging.
- Conjugated nanocomplexes with anti-HER2 antibodies for targeted delivery.
- Utilized immunofluorescence staining and magnetic resonance imaging to confirm specific binding to OVCAR3 cells.
- Irradiated targeted nanocomplexes with near-infrared laser for photothermal ablation of cancer cells.
Main Results:
- Nanocomplex-anti-HER2 conjugates demonstrated specific binding to HER2-overexpressing OVCAR3 cells compared to control MDA-MB-231 cells.
- Photothermal ablation using near-infrared laser irradiation selectively destroyed OVCAR3 cancer cells.
- Both near-infrared light therapy and the nanocomplexes alone were found to be non-cytotoxic in vitro.
Conclusions:
- This study presents the first successful integration of dual modal bioimaging with photothermal cancer therapy for ovarian cancer treatment.
- The developed nanocomplexes show significant promise for image-guided photothermal therapy of ovarian cancer.
- These nanocomplexes are potentially applicable to other HER2-overexpressing cancers.
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