Broadbent, Matthew
(2022)
Development of Gold Nanoparticles for Photodynamic Therapy.
PhD thesis, University of Liverpool.
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Abstract
The mechanistic properties determining whether gold nanoparticle mediated light therapy in human fibroblast cells (HeLa) takes place via a photothermal or photodynamic mechanism are investigated and discussed. The effect of cell size on AuNP uptake is shown, with smaller cells taking up less gold nanoparticles, this leads to a smaller photodynamic dose and lower efficacy of treatment. A new protocol for the investigation of photodynamic efficiency had to be developed for investigating isogenic cell lines UM-SCC-1, UM-SCC-1 pBABE and UM-SCC-1 p53 WT, which have high motility. This protocol was first tested against HeLa cells using citrate-gold nanoparticles, and similar results were obtained as with the original protocol. Due to the extremely low quantum yield for singlet oxygen photogeneration of citrate-gold nanoparticles they are difficult to apply in realistic conditions. Therefore, Gold nanoparticles were loaded with Rose Bengal via a polyelectrolyte layer-by-layer coating. These nanoparticles were characterised and applied as a photodynamic agent. Irradiation of HeLa cells containing these nanoparticles showed increased efficacy compared to citrate-gold nanoparticles, and the effect was successfully modelled to account for beam inhomogeneity, the heterogenous uptake of AuNPs and the photobleaching of Rose Bengal. Rose Bengal loaded gold nanoparticles showed killing in a realistic cell model UM-SCC-1, directly derived from Head-and-Neck cancer cells. When used against isogenic cells lines UM-SCC-1, UM-SCC-1 pBABE (both of which lack the p53 gene, an important regulator of cell metabolism and UM-SCC-1 p53 WT (where the p53 gene has been restored), cells with p53 function were significantly more affected by 1O2. This is consistent with expectations and with dye-mediated photodynamic therapy results reported in literature and confirms the importance of considering the loss of the p53 function which is often encountered in cancerous cells. However, it was also shown that the loss of the p53 function increases gold nanoparticle uptake, counterbalancing the detrimental effect on PDT efficiency.
| Item Type: | Thesis (PhD) |
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| Divisions: | Faculty of Science and Engineering > School of Physical Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 22 Feb 2023 16:24 |
| Last Modified: | 22 Feb 2023 16:24 |
| DOI: | 10.17638/03168490 |
| Supervisors: |
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| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3168490 |
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