Radiotherapy has been used for decades in the treatment of cancer however; the efficacy of radiotherapy is limited by the damage it causes to normal tissue. High Z materials have previously been used as contrast agents in imaging due to their favourable mass attenuation coefficients in comparison to tissue. Gold, a high Z material, has the potential to significantly enhance radiation dose deposited in by physically scattering the energy from the radiation beam. Various publications have demonstrated the potential for gold nanoparticles in enhancing cell death with radiation and calculations predict dose enhancements of two fold or greater. A comparison of various gold nanoparticles showed 1.9 nm Aurovist™ to be the most effective at enhancing cell death in the presence of radiation showing radiosensitisation in MDA-MB-231, DU14S and T98G cancer cell lines not in AGO-1S22, a normal fibroblast cell line. The type of cell death induced is cell line dependent and DNA damage is induced upon exposure to gold nanoparticles alone which is further amplified with radiation. Further investigation observed oxidative stress including ROS production, mitochondrial depolarisation and mitochondrial oxidation as biological responses to gold nanoparticle exposure. Treatment with the ROS scavenger, N-acetyl-cysteine, and gold nanoparticies revealed mitochondrial oxidation as a key event in gold nanoparticle radiosensitisation. Protein disulphide isomerase, an enzyme present on the cell surface, was shown to have a significant role in the cellular effects observed upon gold nanoparticle treatment and radiosensitisation.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:677841 |
| Date | January 2014 |
| Creators | Taggart, L. |
| Publisher | Queen's University Belfast |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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