Near-Infrared Silica-Based Gold Nanoshells as Potential Rapid Diagnostic Imaging Agents For Breast Cancer Tumor Detection
Author
Bickford, Lissett Ramirez
Date
2011Advisor
Drezek, Rebekah A.
Degree
Doctor of Philosophy
Abstract
Although much research has focused on using near-infrared silica-based gold
nanoshells for dual-imaging and therapeutic applications in vivo, these particles may also
prove useful as rapid diagnostic imaging agents for ex vivo applications, such as
intraoperative tumor margin detection. In this thesis, gold nanoshells were successfully
designed to target breast cancer cells through antibodies against the extracellular Human
Epidermal growth factor Receptor 2 (HER2) , whose overexpression is associated with
more aggressive forms of breast cancer. By comparing HER2-positive breast cancer cells
to normal (nonneoplastic) breast cells, the nanoshells effectively labeled HER2-
overexpression within 5 minutes of incubation time. These nanoshells also enhanced contrast of the same cancer cells using two-photon microscopy, which enabled
subsequent validation of preferential labeling using a distinctive co-culture experiment.
To ultimately translate these findings to the clinic, nanoshells of similar design
were studied for their effectiveness at enhancing contrast of malignancy in breast tissue
sections and intact human breast tissue. Through detailed experimental conditions, these
nanoshells increased contrast of cancer cells in sectioned HER2-overexpressing breast
tissue within 5 minutes of incubation time using reflectance confocal microscopy, a
unique imaging capability not previously reported. Finally, these targeted nanoshells
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were used to effectively visualize HER2 receptor expression in intact human breast tissue
specimens within the same 5 minute incubation time point. Through two-photon imaging,
it was shown that these nanoparticies preferentially labeled tissue surface receptors, with
minimal penetration depth. Importantly, the enhanced surface labeling was observed
macroscopically through a standard stereomicroscope and confirmed microscopically
through reflectance confocal microscopy and immunohistochemistry. These results
suggest that anti-HER2-nanoshells used in tandem with a near-infrared reflectance
confocal microscope and a standard stereomicroscope may potentially be used to discern
HER2-overexpressing cancerous tissue from normal tissue in near real time and offer a
rapid supplement to current diagnostic techniques.
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were used to effectively visualize HER2 receptor expression in intact human breast tissue
specimens within the same 5 minute incubation time point. Through two-photon imaging,
it was shown that these nanoparticles preferentially labeled tissue surface receptors, with
minimal penetration depth. Importantly, the enhanced surface labeling was observed
macroscopically through a standard stereomicroscope and confirmed microscopically
through reflectance confocal microscopy and immunohistochemistry. These results
suggest that anti-HER2-nanoshells used in tandem with a near-infrared reflectance
confocal microscope and a standard stereomicroscope may potentially be used to discern
HER2-overexpressing cancerous tissue from normal tissue in near real time and offer a
rapid supplement to current diagnostic techniques.
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Keyword
Engineering; Biomedical engineering; Oncology