Atherosclerosis is the primary reason for Cardiovascular disease, in which arteries become narrowed due to plaque development. Accumulation of low-density lipoprotein (LDL-C) at the site of damage (the endothelium) is known to be a key factor in the pathogenesis of atherosclerosis. By targeting the site of damage, subsequently utilising photothermal therapy should effectively halt or stop the atherosclerotic process. Lipid modifications are known in the literature to increase cellular interactions. Cholesterol is a lipid which can be functionalised onto nanoparticles potentially increasing uptake of gold nanoparticles. This essentially creates a 'fatty nanoparticle' which can also imitate LDL-C, hence being able to target plaques. Herein, the research focus was to investigate the cellular uptake of cholesterol modified nanoparticles and upon success, their capabilities as photothermal agents for targeting plaque sites. Gold nanoparticles were functionalised with cholesterol-DNA.;Thereafter, a series of in vitro studies were carried out using two cell lines: RAWs and HUVECs, to determine cellular uptake. Using 2D and 3D SERRS mapping, the first study determined successful uptake and the second study determined that the uptake was greater in endothelial cells. A 'semi-quantitative' method was applied to calculate the % relative SERRS response from each cell line, allowing for comparisons to be made. Cell viability studies confirmed the non-toxic nature of these probes. In the second part of this research, HGNs were used as the core for these 'fatty nanoparticles' due to their LSPR in the NIR, and commendable photothermal properties. Cholesterol modified HGNs displayed efficient cellular ablation with an in-house photothermal set up. This work successfully provided the basis for using cholesterol modified nanoparticles as photothermal agents in the treatment of CVD.
Date of Award | 18 Jan 2021 |
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Original language | English |
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Awarding Institution | - University Of Strathclyde
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Sponsors | EPSRC (Engineering and Physical Sciences Research Council) |
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Supervisor | Duncan Graham (Supervisor) & Karen Faulds (Supervisor) |
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