Award Date

5-1-2015

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Health Physics and Diagnostic Sciences

First Committee Member

Steen Madsen

Second Committee Member

Yu Kuang

Third Committee Member

Bing Ma

Fourth Committee Member

Robbin Hickman

Number of Pages

67

Abstract

Technological advances in the ability to construct and manipulate nanoscale particles have opened up the possibility of using solid metallic nanoparticles and mixed metal nanoshells as a means to increase dose enhancement and treatment efficacy to tumors. In order for nanoparticles to be an effective form of treatment, they must be delivered to tumors in sufficient concentrations so that there is a dose enhancement factor due to ionizing radiation, as well as being essentially non-toxic to healthy cells. Gold nanoparticles and silica-gold nanoshells fit these requirements. Gold has a high atomic number (Z=79), which gives a larger cross section for the photoelectric effect vs. tissue with regards to kilovoltage x-rays. Both gold and silica are also relatively inert and biocompatible.

The investigation of dose enhancement to cells that have been incubated with nanoparticles and nanoshells is the focus of this thesis. The effectiveness of the treatment was determined by measuring the size of multicellular hybrid spheroids consisting of human glioma cells and murine lymphocytic monocytes. Dose enhancement effects was also examined in murine lymphocytic monocytes using an MTS assay, which measures metabolic activity in cells.

A clear dose response was observed for spheroids consisting of human glioma cells only: increasing doses resulted in decreased spheroid growth. With a few exceptions, this trend was also observed in hybrid spheroids consisting of glioma cells and nanoparticle or nanoshell loaded monocytes. Contrary to the premise of utilizing the photoelectric effect, the most pronounced dose effect was observed in the pure glioma irradiated spheroids which showed greater growth suppression compared to the nanoparticle and nanoshell loaded hybrid spheroids at each dose investigated. A similar trend was found when comparing the viability of bare and nanoparticle/nanoshell loaded monocytes exposed to kilovoltage x-rays. These results are considered anomalous since kilovoltage x-rays are expected to be more damaging to cells and spheroids containing nanoparticles/nanoshells due to enhanced photoelectric absorption. The anomalous results were attributed to inaccuracies in x-ray tube output.

Optimization of MTS parameters required for accurate determination of monocyte viability represents the most significant finding of this work. It was found that 50,000 cells per well yielded an accurate MTS signal. Furthermore, the MTS assay should not be performed less than 96 hours from the time of irradiation. As long as this 96 hour criterion is satisfied, any of the investigated MTS incubation times (1 – 4 hours) can be used. Finally, at the concentrations used in these studies, neither nanoparticles nor nanoshells were toxic to murine lymphocytes.

Keywords

Gold; Gold Nanoparticles; Gold Silica; In Vitro; Kilovoltage X-Rays; Nanoparticles; Nanoshells; Radiosensitization

Disciplines

Biophysics | Nanoscience and Nanotechnology

Language

English


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