Design and Applications of Gold Nanoparticles for Ion Sensing and Cancer Therapeutics

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dc.contributor.advisorLee, Jiyong
dc.creatorYoun, Jonghae
dc.date.accessioned2020-07-06T21:19:40Z
dc.date.available2020-07-06T21:19:40Z
dc.date.created2019-05
dc.date.issued2019-04-23
dc.date.submittedMay 2019
dc.date.updated2020-07-06T21:19:41Z
dc.description.abstractGold nanoparticles have been studied extensively because their size- and shape-dependent chemical, physical, and optical characteristics, as well as, their surface chemistry that makes them a more powerful tool in a variety of fields. In this dissertation, two studies were carried out to design new gold nanoparticles by selecting the appropriate size, shape, and surface ligands for cancer therapy and metal ion sensing. In the first project, I developed a novel gold nanorod that selectively targets and ablates cancer stem cells (CSCs) via photothermal therapy. CSCs have been identified as a new target for cancer therapy due to their unique characteristics of tumor initiation, recurrence, metastasis, and drug resistance. Despite extensive research that has provided new targets, technologies, and tools for CSC treatment, the practical use of these is limited. Herein, I report that gold nanorods by functionalized with the CL-1-19-1 ligand selectively binds to CSCs versus non-CSCs, and they can decrease CSC populations via laser-induced photothermal therapy. I demonstrated that gold nanorods bound to an Aldehyde dehydrogenase (ALDH) positive subpopulation rather than Aldehyde dehydrogenase negative subpopulation. Breast cancer cells treated with gold nanorods following laser irradiation (the nanosecond pulsed laser at 532 nm) showed decreased number of ALDH positive cells (>50% compared to control group) and diminished expressions of CSCassociated transcription factors. Thus, these results suggested an effective platform to eradicate CSCs. In the second project, I took advantage of the reduction capability of tyrosine at alkaline conditions to develop peptide-templated fluorescent gold nanoclusters (AuNCs). In order to better understand the role of tyrosine in forming fluorescent AuNC, tripeptides, tyrosine-cysteine-tyrosine (YCY) and serine-cysteine-tyrosine (SCY), were designed and prepared. Then under a pH of 10 and 70 °C, we obtained AuNCs of blue and red fluorescence from YCY peptide and the AuNC of blue fluorescence from SCY peptide. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) revealed that peptide-templated AuNCs possessed a spherical shape and narrow particle size distribution in aqueous solution. Furthermore, I found that the fluorescence of blueemitting YCY- and SCY-AuNCs is quenched with Fe³⁺ and Cu²⁺ in a wide liner range, while the fluorescence of the red-emitting YCY-AuNC are stable in 13 different metal ion solutions. Interestingly, blue-YCY-AuNC was more than doubly responsive to Fe³⁺ compared to SCY-AuNC presumably due to the presence of two tyrosine residues, causing enhanced aggregation propensity under the presence of Fe³⁺ in DLS measurement. These results thus suggest the chelation effect between the peptide on the AuNC surface and the target ion resulted in aggregation, which was found to cause fluorescence quenching. In addition, the DLS data demonstrates that the aggregation propensity is closely related to the sensitivity of the sensing system to the target metal
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/10735.1/8682
dc.language.isoen
dc.rights©2019 Jonghae Youn. All Rights Reserved.
dc.subjectStem cells
dc.subjectCancer cells
dc.subjectFever
dc.subjectHeat--Physiological effect
dc.subjectFluorescence
dc.subjectPhotothermal spectroscopy
dc.titleDesign and Applications of Gold Nanoparticles for Ion Sensing and Cancer Therapeutics
dc.typeDissertation
dc.type.materialtext
thesis.degree.departmentChemistry
thesis.degree.grantorThe University of Texas at Dallas
thesis.degree.levelDoctoral
thesis.degree.namePHD

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