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aff1d4bb7a70d34bff3ea8299a137e04 |
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Date |
2019-04-08 |
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repository |
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abstract |
Nanotechnology offers vital tools for cancer diagnosis, early detection and novel
treatments. Gold nanoparticles (AuNPs) are at the forefront of biological and biomedical
research and show an increased promise in targeted cancer therapy due to their unique
physicochemical properties. They offer the advantage of biomolecular interaction both
at the cell surface level and inside the cell.
In this thesis, 2nm AuNPs surface functionalised with a 50:50 ratio of a thiolated
α-Galactose derivative and a thiol-PEGamine were examined for their toxicity and uptake
in normal and cancer cell lines in vitro. Using this simple ligand structure, a selective
cancer toxicity was observed, which was highly dependent upon the nanoparticles’ synthesis
duration. This observation was correlated to ligand density, which decreased with
shorter synthesis time, making particles less toxic. Detailed insight into the mechanism
of toxicity and uptake was gained by energy-dependent experiments and cell death assays,
revealing a significant adhesion of these particles to filopodia. The proposed mechanism
of cell death in HSC oral squamous carcinoma cells exposed to AuNPs was identified
to be the extrinsic apoptotic pathway, as toxicity was abrogated by inhibition of
either caspase 3/7 or caspase 8, but not by inhibition of caspase 9.
Future directions include batch standardisation of the optimum nanoparticle synthesis
conditions and elucidation of the mechanisms of cell uptake and toxicity in a variety
of cancer and normal cell lines. |
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authorList |
authors |
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degree |
phd |
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status |
unpublished |
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status |
nonPeerReviewed |
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uri |
http://data.open.ac.uk/oro/document/835705 |
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uri |
http://data.open.ac.uk/oro/document/835706 |
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uri |
http://data.open.ac.uk/oro/document/835711 |
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uri |
http://data.open.ac.uk/oro/document/835712 |
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uri |
http://data.open.ac.uk/oro/document/835713 |
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uri |
http://data.open.ac.uk/oro/document/835714 |
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uri |
http://data.open.ac.uk/oro/document/835815 |
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uri |
http://data.open.ac.uk/oro/document/835816 |
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uri |
http://data.open.ac.uk/oro/document/835817 |
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uri |
http://data.open.ac.uk/oro/document/835818 |
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uri |
http://data.open.ac.uk/oro/document/835819 |
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uri |
http://data.open.ac.uk/oro/document/835820 |
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uri |
http://data.open.ac.uk/oro/document/835822 |
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uri |
http://data.open.ac.uk/oro/document/840296 |
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uri |
http://data.open.ac.uk/oro/document/840297 |
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uri |
http://data.open.ac.uk/oro/document/840391 |
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uri |
http://data.open.ac.uk/oro/document/841588 |
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type |
Article |
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type |
Thesis |
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label |
Tzelepi, Konstantina Nadia (2019). Mechanisms of Nanoparticle Toxicity in Cancer
and Normal Cells. PhD thesis The Open University. |
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label |
Tzelepi, Konstantina Nadia (2019). Mechanisms of Nanoparticle Toxicity in Cancer
and Normal Cells. PhD thesis The Open University. |
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Title |
Mechanisms of Nanoparticle Toxicity in Cancer and Normal Cells |
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in dataset |
oro |