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dc.contributor.advisor West, Jennifer L.
dc.creatorCoughlin, Andrew
dc.date.accessioned 2013-09-16T14:59:44Z
dc.date.accessioned 2013-09-16T15:00:08Z
dc.date.available 2013-09-16T14:59:44Z
dc.date.available 2013-09-16T15:00:08Z
dc.date.created 2013-05
dc.date.issued 2013-09-16
dc.date.submitted May 2013
dc.identifier.urihttps://hdl.handle.net/1911/71941
dc.description.abstract Cancer accounts for nearly 1 out of every 4 deaths in the United States, and because conventional treatments are limited by morbidity and off-target toxicities, improvements in cancer management are needed. This thesis further develops nanoparticle-assisted photothermal therapy (NAPT) as a viable treatment option for cancer patients. NAPT enables localized ablation of disease because heat generation only occurs where tissue permissive near-infrared (NIR) light and absorbing nanoparticles are combined, leaving surrounding normal tissue unharmed. Two principle approaches were investigated to improve the specificity of this technique: multimodal imaging and molecular targeting. Multimodal imaging affords the ability to guide NIR laser application for site-specific NAPT and more holistic characterization of disease by combining the advantages of several diagnostic technologies. Towards the goal of image-guided NAPT, gadolinium-conjugated gold-silica nanoshells were engineered and demonstrated to enhance imaging contrast across a range of diagnostic modes, including T1-weighted magnetic resonance imaging, X-Ray, optical coherence tomography, reflective confocal microscopy, and two-photon luminescence in vitro as well as within an animal tumor model. Additionally, the nanoparticle conjugates were shown to effectively convert NIR light to heat for applications in photothermal therapy. Therefore, the broad utility of gadolinium-nanoshells for anatomic localization of tissue lesions, molecular characterization of malignancy, and mediators of ablation was established. Molecular targeting strategies may also improve NAPT by promoting nanoparticle uptake and retention within tumors and enhancing specificity when malignant and normal tissue interdigitate. Here, ephrinA1 protein ligands were conjugated to nanoshell surfaces for particle homing to overexpressed EphA2 receptors on prostate cancer cells. In vitro, successful targeting and subsequent photothermal ablation of prostate cancer cells was achieved with negligible nanoshell binding to normal cells. In vivo however, ephrinA1-nanoshells did not promote enhanced therapeutic outcomes in mice bearing subcutaneous prostate cancer tumors treated with NAPT compared to nontargeted particles. Nonetheless, both treatment groups demonstrated effective ablation of prostate tumors, as evidenced by tumor tissue regression. Further investigation is warranted to overcome probable protein immunogenicity that offsets ephrinA1 targeting in vivo. With future study, photothermal therapy with multimodal gadolinium-conjugated and molecularly targeted nanoshells may offer a viable treatment option for cancer patients in the clinic.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.subjectNanoshells
Gadolinium
Multimodal imaging
Cancer
Photothermal therapy
dc.title Gold Nanoconstructs for Multimodal Diagnostic Imaging and Photothermal Cancer Therapy
dc.contributor.committeeMember Drezek, Rebekah A.
dc.contributor.committeeMember Hafner, Jason H.
dc.date.updated 2013-09-16T15:00:08Z
dc.identifier.slug 123456789/ETD-2013-05-433
dc.type.genre Thesis
dc.type.material Text
thesis.degree.department Bioengineering
thesis.degree.discipline Engineering
thesis.degree.grantor Rice University
thesis.degree.level Doctoral
thesis.degree.name Doctor of Philosophy
dc.identifier.citation Coughlin, Andrew. "Gold Nanoconstructs for Multimodal Diagnostic Imaging and Photothermal Cancer Therapy." (2013) Diss., Rice University. https://hdl.handle.net/1911/71941.


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