Modulating Gold Nanoparticle in vivo Delivery for Photothermal Therapy Applications Using a T Cell Delivery System

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dc.contributor.advisorDrezek, Rebekah A.en_US
dc.creatorKennedy, Laura Carpinen_US
dc.date.accessioned2013-03-08T00:34:57Zen_US
dc.date.available2013-03-08T00:34:57Zen_US
dc.date.issued2012en_US
dc.description.abstractThis thesis reports new gold nanoparticle-based methods to treat chemotherapy-resistant and metastatic tumors that frequently evade conventional cancer therapies. Gold nanoparticles represent an innovative generation of diagnostic and treatment agents due to the ease with which they can be tuned to scatter or absorb a chosen wavelength of light. One area of intensive investigation in recent years is gold nanoparticle photothermal therapy (PTT), in which gold nanoparticles are used to heat and destroy cancer. This work demonstrates the utility of gold nanoparticle PTT against two categories of cancer that are currently a clinical challenge: trastuzumab-resistant breast cancer and metastatic cancer. In addition, this thesis presents a new method of gold nanoparticle delivery using T cells that increases gold nanoparticle tumor accumulation efficiency, a current challenge in the field of PTT. I ablated trastuzumab-resistant breast cancer in vitro for the first time using anti-HER2 labeled silica-gold nanoshells, demonstrating the potential utility of PTT against chemotherapy-resistant cancers. I next established for the first time the use of T cells as gold nanoparticle vehicles in vivo. When incubated with gold nanoparticles in culture, T cells can internalize up to 15000 nanoparticles per cell with no detrimental effects to T cell viability or function (e.g. migration and cytokine secretion). These AuNP-T cells can be systemically administered to tumor-bearing mice and deliver gold nanoparticles four times more efficiently than by injecting free nanoparticles. In addition, the biodistribution of AuNP-T cells correlates with the normal biodistribution of T cell carrier, suggesting the gold nanoparticle biodistribution can be modulated through the choice of nanoparticle vehicle. Finally, I apply gold nanoparticle PTT as an adjuvant treatment for T cell adoptive transfer immunotherapy (Hyperthermia-Enhanced Immunotherapy or HIT) of distant tumors in a melanoma mouse model. The results presented in this thesis expand the potential of gold nanoparticle PTT from only chemotherapy-sensitive or localized cancers to chemotherapy-resistant non-localized cancers that currently defy conventional therapies.en_US
dc.format.extent188 p.en_US
dc.format.mimetypeapplication/pdfen_US
dc.identifier.callnoTHESIS BIOENG. 2012 KENNEDYen_US
dc.identifier.citationKennedy, Laura Carpin. "Modulating Gold Nanoparticle in vivo Delivery for Photothermal Therapy Applications Using a T Cell Delivery System." (2012) Diss., Rice University. <a href="https://hdl.handle.net/1911/70290">https://hdl.handle.net/1911/70290</a>.en_US
dc.identifier.digitalKennedyLen_US
dc.identifier.urihttps://hdl.handle.net/1911/70290en_US
dc.language.isoengen_US
dc.rightsCopyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.en_US
dc.subjectHealth sciencesen_US
dc.subjectEnvironmental scienceen_US
dc.subjectApplied sciencesen_US
dc.subjectT cellsen_US
dc.subjectGold nanoparticlesen_US
dc.subjectPhotothermal therapyen_US
dc.subjectImmunotherapyen_US
dc.subjectDrug deliveryen_US
dc.subjectCancer treatmenten_US
dc.subjectBiomedical engineeringen_US
dc.subjectNanoscienceen_US
dc.subjectImmunologyen_US
dc.subjectOncologyen_US
dc.titleModulating Gold Nanoparticle in vivo Delivery for Photothermal Therapy Applications Using a T Cell Delivery Systemen_US
dc.typeThesisen_US
dc.type.materialTexten_US
thesis.degree.departmentBioengineeringen_US
thesis.degree.disciplineEngineeringen_US
thesis.degree.grantorRice Universityen_US
thesis.degree.levelDoctoralen_US
thesis.degree.nameDoctor of Philosophyen_US
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