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Title: Gold nanoparticle dose enhancement and plasma induced cellular damage
Author: Muir, M. F.
ISNI:       0000 0004 2745 212X
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2013
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Targeting the dose delivered to cancer cells while minimizing damage to sur- rounding healthy tissue is the primary objective of radiotherapy. To achieve this multiple beams of X-rays with MeV energies are collimated to match the shape of a target volume, improving the contrast ratio between the dose to cancerous cells against the dose to healthy cells. Another possibility which has been explored is the use of materials with a high atomic number to preferentially enhance dose, due to their increased photoelectric absorption of keV energy X-rays. By using nanoparticles of these high Z elements it is possible to distribute them at the sub-cellular level. The work presented in this thesis investigates the dose en- hancement due to the addition of spherical nanoparticles of gold in vitro, for a range of monoenergetic kilovoltage X-rays. In order to perform these studies an X-V translation system was constructed which allowed samples to be manipulated in a horizontal beam of X-rays pro- duced from a synchrotron. Samples were rastered through a beam of X-rays at a pre-calculated rate which was determined from an in-line dosimeter. Control of the target dose was possible by adjusting the rate samples were shuttled through the beam. This translation system was used to irradiate both y-H2,AX and clone- genic assays in order to investigate the effect of monoenergetic X-ray driven gold nanoparticle dose enhancement. Manual counts of the mean number of foci per cell from the y-H2AX assay showed an energy dependent dose enhancement due to gold that was inconsistent . with a macroscopic model of dose. The development of an analysis algorithm to determine the nuclear distribution of damage, along with a microscopy technique which exploits the surface plasmon resonances of gold, gave information about mechanism. These studies found that the location of gold nanoparticles and 2the range of electrons emitted when ionized, are significant factors behind the observed energy dependance. The results from clonoqenic studies found there was a significant enhancement in the formation of single lethal events for irradiated cells with gold. There was little enhancement in the production of sub-lethal events for the same group of cells. These findings also deviate from a macroscopic dose enhancement model. Application of a local effect model, which considers the nanodosimetry around a gold particle, provides an explanation for these observations. An opportunity arose during this thesis to study the effect liquid produced plasmas have on cells. Using a submerged electrode, monolayers of cells were exposed to an electrical discharge plasma and the effects were measured using both the y-H2AX and clonogenic assays. Generating a plasma produces many of the damaging agents produced by X-ray irradiation (such as electrons and radicals). Studies showed that the cells responded similarly when exposed to plasmas or X-rays, yielding Poissonian distributions of nuclear double strand breaks, and a linear quadratic dependance of cell death. The results presented here would be useful as a first step in the assessment of risk from plasma exposure compared to a known standard like X-rays.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available