Radiosensitization of cell sub-populations by gold nanoparticles cross-correlative microscopy for elucidating fundamental mechanisms /
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(Published version)
Date
2017
Authors
Turnbull, Tyron James,
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thesis
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Abstract
Nanoparticles have been demonstrated to enhance the effects of radiotherapy; however, to improve therapeutic outcomes requires optimization of their formulation. Optimization and hence clinical translation of nanoparticles as radiosensitizing agents is a complex research topic, primarily due to an incomplete understanding of the underlying mechanisms leading to the observed radio sensitization effects along with the inherent heterogeneity of biological systems. Presented in this thesis is a methodology that has been developed to quantify the uptake of gold nanoparticles (AuNPs) at the single cell level using synchrotron x-ray fluorescence microscopy (XRF) and correlation of these measurements with DNA double strand breaks quantified using the γH2AX foci assay from confocal microscopy in the same cell populations. Uptake of 14nm polyethylene glycol (PEG) AuNPs was found to have a high level of intercellular heterogeneity between multiple cell lines (PC-3, CaCo2 and MDA-MB-231) and 2 nanoparticle co-culture times (30 mins and 10% of the respective cell line doubling time). Histograms of uptake data were all well described by a lognormal distribution for all conditions. This intercellular heterogeneity was shown to have biological consequence with PC-3 cells containing larger quantities of AuNPs being more susceptible to cell death post x-ray irradiation from a 6MV clinical linear accelerator.
School/Discipline
University of South Australia. Future Industries Institute.
Future Industries Institute.
Future Industries Institute.
Dissertation Note
Thesis (PhD(Biomaterials Engineering and Nanomedicine))--University of South Australia, 2017.
Provenance
Copyright 2017 Tyron James Turnbull.
Description
1 ethesis (xx, 193 pages) :
illustrations (some colour)
Includes bibliographical references (pages 163-173)
illustrations (some colour)
Includes bibliographical references (pages 163-173)
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