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Nanoparticle Enhanced Radiotherapy

Ahmad, Reem Hussain Ali; (2019) Nanoparticle Enhanced Radiotherapy. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Nanoparticles have been shown to create a localised increase in dose deposition when combined with ionising radiation. Although this has been shown in the literature, there are several factors that can alter the level of enhancement, which need to be investigated before translating the use of nanoparticles for clinical treatments. This thesis aims to investigate three different aspects of this effect: (i) effect of nanoparticles when combined with proton therapy, (ii) study the combined effect of nanoparticle material, size and beam energy with photon irradiation, (iii) consider the biological impact with different cell lines, nanoparticle parameters and radiation types. To consider the effect of nanoparticles with protons, Monte Carlo simulations were developed to model the effects of nanoparticle concentrations. The use of nanoparticles at clinically relevant concentrations was shown to cause an effect on the Bragg peak, where changes were quantified in the model and validated experimentally. Both simulation and experiment demonstrated a shift in the distal edge of the Bragg peak, with a simulated shift of 4.5 mm compared to a measured shift of 2.2 mm with a beam of 226 MeV protons. To study the combined effect, another model was developed, studying the effect on dose deposition around a single nanoparticle with photon irradiation. Here the geometry could be altered such that the nanoparticle size and material were studied, as well as the effect of different incident beam energies. These simulations considered the effects on multiple scales to determine the extent of the enhancement, where it is then possible to inform where nanoparticles need to be localised to within a cell to observe the most beneficial effect. The highest level of enhancement was found with 2 nm gold nanoparticles and 90 keV photons. Finally to investigate the biological impact, an in vitro model was used with different cell lines, nanoparticles and radiation types, to gain an understanding of the biological effects. This was able to show differences in cell survival when comparing different cell lines, with different levels of radiosensitivity. As well as this, differences in DNA damage were shown when comparing X-ray radiotherapy and proton therapy. In terms of enhancement, gold nanoparticles were shown to be more effective with MCF-7 cells, whereas gadolinium based nanoparticles caused more cell kill for U87 cells.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Nanoparticle Enhanced Radiotherapy
Event: UCL (University College London)
Language: English
Additional information: Copyright © The Author 2019. Original content in this thesis is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request.
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Targeted Intervention
URI: https://discovery.ucl.ac.uk/id/eprint/10067852
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