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.
dc.creatorKennedy, Laura Carpin
dc.date.accessioned2013-03-08T00:34:57Z
dc.date.available2013-03-08T00:34:57Z
dc.date.issued2012
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.
dc.format.extent188 p.en_US
dc.format.mimetypeapplication/pdf
dc.identifier.callnoTHESIS BIOENG. 2012 KENNEDY
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>.
dc.identifier.digitalKennedyLen_US
dc.identifier.urihttps://hdl.handle.net/1911/70290
dc.language.isoeng
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.
dc.subjectHealth sciences
dc.subjectEnvironmental science
dc.subjectApplied sciences
dc.subjectT cells
dc.subjectGold nanoparticles
dc.subjectPhotothermal therapy
dc.subjectImmunotherapy
dc.subjectDrug delivery
dc.subjectCancer treatment
dc.subjectBiomedical engineering
dc.subjectNanoscience
dc.subjectImmunology
dc.subjectOncology
dc.titleModulating Gold Nanoparticle in vivo Delivery for Photothermal Therapy Applications Using a T Cell Delivery System
dc.typeThesis
dc.type.materialText
thesis.degree.departmentBioengineering
thesis.degree.disciplineEngineering
thesis.degree.grantorRice University
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy
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