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Durham e-Theses
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Biological and Photophysical Analysis of Novel Diphenylacetylene Photosensitisers for the treatment of Oral Epithelial Dysplasia

HUGHES, JOSHUA,GRAHAM (2024) Biological and Photophysical Analysis of Novel Diphenylacetylene Photosensitisers for the treatment of Oral Epithelial Dysplasia. Doctoral thesis, Durham University.

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Abstract

Oral cancer is the sixth most common cancer in the world. Diagnosis often occurs at the later stages of disease progression, which is a large contributing factor to the survival rate being below 50% over a five-year period. The conventional method of treatment surgery and radiotherapy, is highly invasive with large implications to patient’s quality of life. Photosensitisers provide a highly-targeted, non-invasive, treatment for cancerous and pre-cancerous lesions, either as an alternative to, or in combination with established procedures. A novel class of donor-acceptor diphenylacetylene photosensitisers have been developed by LightOx. The varied structure of the donor and accepting groups have implications on lipophilicity, induced charge-transfer and subsequent cellular localisation and phototoxicity. Compounds with small charge-transfer characteristics, combined with heavy-atoms, such as the sulfur atom in thiophene groups proved to be the most potent. Futhermore, non-polar, lipophilic environments were optimal to induce phototoxicity for this class of photosensitisers. Thus compounds with log $D$ > 4 were the most potent, localising to lipid droplets, lysosomes, and membranes in the peri-nuclear region. Additionally, the compounds were studied for multi-photon FLIM, FluoRaman, and photodynamic diagnostic capabilities.

Item Type:Thesis (Doctoral)
Award:Doctor of Philosophy
Faculty and Department:Faculty of Science > Physics, Department of
Thesis Date:2024
Copyright:Copyright of this thesis is held by the author
Deposited On:04 Jun 2024 12:29

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