Thesis
Use of raman spectroscopy for the study of brain tumours
- Creator
- Rights statement
- Awarding institution
- University of Strathclyde
- Date of award
- 2021
- Thesis identifier
- T16046
- Person Identifier (Local)
- 201674424
- Qualification Level
- Qualification Name
- Department, School or Faculty
- Abstract
- Every year in the UK, there are over 12,000 new brain, central nervous system (CNS) and intracranial tumour cases diagnosed. The main treatment methods for brain tumours are surgery, radiation therapy and chemotherapy. The aim of radiation therapy is to damage the deoxyribonucleic acid (DNA) of the cancer cells thereby preventing the cells from continuing to grow and divide, however the main limitation is the collateral damage to healthy cells surrounding the tumour. For that reason, the overall radiation dose must be kept low (1 – 2 Gy single fractions), leading to long treatment times and potentially ineffective treatment. These limitations have led to a drive towards patient-specific radiation therapy including ways to predict treatment response and tumour radiation resistance, monitor treatment response and localise treatment dose to the tumour cells. The aim of this thesis is to assess the use of Raman spectroscopy as a method for monitoring changes in UVW human glioma cells related to the cell cycle and the treatment response of UVW cells to radiation therapy. This work also aims to assess gold nanoparticles (AuNPs) as potential radiosensitising agents and to investigate how the nanoparticles’ properties including size, shape and surface chemistry, affect their radiation enhancing abilities. Raman spectroscopy was used to differentiate between UVW cells synchronised to different points of the cell cycle (early G1 phase, G1/S boundary, S phase and G2/M boundary). Raman spectroscopy was able to differentiate between cells in these phases with the largest difference observed for cells at the G2/M boundary. The spectral differences were assigned to changes in protein and nucleic acid levels in the cells. Stimulated Raman scattering (SRS) imaging was used to monitor the cell division of synchronised UVW cells in real-time. This work demonstrated the potential of SRS for live cell imaging of real-time cellular changes. Raman spectroscopy was then used to investigate the difference between the radiation response (6 Gy) of unsynchronised UVW cells compared to UVW cells synchronised to the G1/S boundary where cells are known to display radiation resistance. Differences in radiation response profile between the different sample groups were demonstrated with a larger response in the unsynchronised cells observed. The radiation response was attributed to differences in spectral protein levels in the cells, potentially due to the repair mechanisms occurring in the cells. Finally, this work assessed the use of different types of AuNPs as radiosensitising agents in combination with radiation therapy (0 – 6 Gy). Gold nanospheres (AuNP35 & AuNP55), hollow gold nanoparticles (HGN) and gold nanostars (AuNS) were compared. These all demonstrated successful radiosensitisation, with AuNS displaying the best enhancement. However, the different types of AuNPs displayed large variation in stability, cellular uptake and cellular toxicity. Functionalising the surface of the AuNPs with polyethylene glycol (MT-PEG) was studied to attempt to improve the stability and biocompatibility of the nanoparticles when they were introduced to the UVW cells. This functionalisation was shown to improve stability however the cellular uptake was also hindered for all types of AuNPs. Overall, this work highlights the use of Raman spectroscopy as a useful tool for monitoring changes to UVW cells related to cell cycle variation and radiation response. In addition, AuNPs were shown as effective tools for enhancing and localising the radiation dose in UVW cells. The properties of these nanoparticles including their size, shape and surface functionalisation were shown to have a large influence on the radiosensitising properties. The effect of these properties creates scope for further work to optimise the nanoparticles as radiosensitising agents.
- Advisor / supervisor
- Faulds, Karen.
- Boyd, Marie.
- Resource Type
- DOI
- Funder
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File | 2021-11-10 | Embargo |