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Title: Subcellular imaging and radiation effects of gold nanoparticles in tumour cells
Author: McQuaid, Harold Nelson
ISNI:       0000 0004 6058 9179
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2016
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Preclinical studies have demonstrated the radiosensitisation of tumour cells with X-ray radiation via treatment with gold nanoparticles (GNPs). Dose enhancement is achieved from the increased absorption of a high Z element such as gold in comparison to soft tissue. Variation however, between theoretical predictions of radioenhancment and experimental measurement is significant enough that the mechanisms leading to an increase in cell killing and DNA damage are still not clear. Using a newly developed intracellular GNP imaging technique that combines multiphoton fluorescent lifetime imaging and conventional confocal microscopy, this thesis investigated the cellular uptake, intracellular distribution and damage enhancement of GNPs. Intracellular uptake and distribution of GNPs were found to vary greatly depending on the cell line/GNP combination. The irradiation of intracellular GNPs with synchrotron-generated monoenergetic X-rays produces a shower of secondary electrons possessing well characterised energies and ranges. Using this knowledge a DNA damage model was generated that included the production of these intermediate electrons. The model successfully accounted for the variation in DNA damage enhancement with varying X-ray energy thereby proposing a mechanism behind GNP damage enhancement. Experimental cell survival results were also shown to follow the outcome predicted by the Local Effect Model. It was therefore possible to show for the first time good agreement between experimental measurements of cell killing and DNA damage due to GNP enhancement, with the biological outcomes predicted by the LEM and the DNA damage model. The requirement of two distinct models, one for short-term DNA damage and another for cell survival, indicates that for GNP enhancement two separate damage mechanisms are present. Despite equating short term DNA damage to the dose deposited by photoelectrons, it was found not to be an accurate indicator of long term cell survival. Long term cell survival was determined to be driven by secondary Auger electrons.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available