published_or_final_version / abstract / Chemistry / Doctoral / Doctor of Philosophy

published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy

published_or_final_version / abstract / Chemistry / Doctoral / Doctor of Philosophy

published_or_final_version / abstract / Chemistry / Doctoral / Doctor of Philosophy

Vaccination is one of the most effective public health interventions in the world, saving millions of lives and preventing the onset of debilitating diseases. With widespread emergence of multi-drug resistant pathogens, the importance of preventative medicine has become even more apparent. However, one of the limiting factors in developing novel vaccines that are both safe and highly immunogenic is the availability of adjuvant delivery systems licensed for human use. The purpose of this study was to investigate the role gold nanoparticles could play as an effective vaccine delivery system. A variety of coupling chemistries were explored for their ability to conjugate protein and polysaccharide antigens onto the surface of gold nanoparticles for the development of vaccines against a number of biologically important human pathogens including Y. pestis, B. mallei and S. pneumoniae. Retention of antigenicity and coupling efficiency of conjugated molecules was measured using characterisation techniques such as localised surface plasmon resonance and immunoblotting. Gold nanoparticle coupled antigens were then used to immunise mice and to measure the protective efficacy and the immunological response induced. The findings indicate antigen-specific immune responses are elevated when an antigen is coupled onto gold nanoparticles. Moreover, immunological data from nanoparticle coupled glycoconjugate vaccines against B. mallei and S. pneumoniae indicate the likely presence of a strong T cell immune response which is essential for providing immunological memory. Finally, an intracellular trafficking assay was carried out to identify some of the mechanisms that might be involved in uptake of gold nanoparticles into professional phagocytes. Confocal imaging of receptors associated with endosomal compartments revealed that gold nanoparticles may enter cells through multiple pathways. The findings reported in this study suggest that gold nanoparticles may be an excellent candidate for further investigation as a novel vaccine delivery system.

Cancer is one of the most notorious diseases affecting the human population today with very few effective treatments. Due to the disparate nature of cancers, it is difficult to obtain a treatment that can cure cancer. Thus, there is a large influx of research towards cancer therapies, leading to one of the discovery that cancer cells (tumors) have a low thermotolerance in comparison to normal cells. If the temperature of the cancer cells is increased into the hyperthermia range (~45°C) thermal damage occurs, causing cell death by protein denaturation and membrane disruption. A recent development in this field has been in the photothermal treatment of tumors, which is starting to utilize plasmonic particles to enhance the specificity of the treatment. The plasmonic nanoparticles, specifically gold, can reach the tumor site using passive targeting and when irradiated with a tuned laser will emit heat localized to a small region around the nanoparticle killing the surrounding cancer cells. This process has been shown to reduce tumor size in vivo with gold nanoshells and gold nanorods. However, it has not been shown which particle is better at delivering the heat to the tumor site. Therefore in this study, it will be shown which particle generates the most heat. Solutions of tissue simulating phantom and different concentrations of nanoparticles were irradiated with a laser to measure the increase in temperature. Additionally, simulations were performed using Mie Theory for nanoshells and the Discrete Dipole Approximation for nanorods. Based on the physical parameters of the nanoshells and nanorods used in this experiment, the adjusted absorption cross-section was determined. It was found that nanoshells generated the most amount of heat on a per particle basis, and that it was necessary to have a nanorod concentration of 5.5 times the concentration of nanoshells to generate the same amount of heat as nanoshells. These results were confirmed using Monte Carlo and Finite Difference Modeling of the nanoparticle heating experiments. However, the choice of nanoparticle still depends on the application and the targeting efficiency in vivo. / text

Glycerol is a very promising alternative fuel to hydrogen in fuel cells. However, the utilisation of glycerol as a fuel requires a good catalyst, due to the slow kinetics of glycerol electrooxidation. Gold has been identified as a promising catalyst due to its high activity and stability for glycerol electrooxidation – although the overpotentials are higher than on platinum and palladium. Modification of a nano-Au/C catalyst by the addition of MnO2, in an attempt to further improve the activity and lower the overpotential for glycerol oxidation, was therefore first explored. This was followed by investigations into the effects of gold particle size and loading. Finally, the effect of gold particle size on oxidation of gold-catalysed glycerol oxidation intermediates was also briefly explored. Studies into MnO2 addition showed that the pre-deposition of MnO2 yielded catalysts with smaller, more uniform gold particles, and catalysts with MnO2 contents of 5 and 9 wt % had higher mass activities and lower onset- and peak- potentials than Au/C. All the Au/xMnO2/C catalysts were more active than the palladium- and platinum-based catalysts reported in literature, which effectively demonstrated the advantage of using a gold-based catalyst for glycerol oxidation – especially when supported by MnO2 which lowered the overpotential for glycerol oxidation over gold. For the study into gold particle size, small gold particles of average diameter ≤ 4.7 nm had higher gold mass-based activities than medium-sized (14.7 nm) particles and were at least twice as active as catalysts containing large (≥ 43 nm) gold particles. The small gold particles also gave lower glycerol oxidation onset potentials, which was attributed to the predominance of Au(110) planes on those particles. Glycerol oxidation also appeared to proceed further along the oxidation pathway over small gold particles, which was confirmed in preliminary studies into the oxidation of glycerol oxidation intermediates. However, specific activity increased with increasing gold particle size, due mainly to the higher intrinsic activity of the Au(111) plane, which increased relative to Au(110) with increasing gold particle size. The important requirements for fuel cell applications are factors such as high mass activity, low overpotentials and high stability – all of which were met by the catalysts containing small gold particles defined by predominantly Au(110) facets. Investigations into the gold loading effect showed similar mass- and specific- activities for catalysts with 5-20 % gold loading. However, only the catalysts with higher gold loadings (15-20 %) did not deactivate early during CV, indicating that a larger gold surface area is necessary to resist poisoning at high potentials. On the basis of low onset potentials, high mass activity, and stability at low overpotentials, a minimum gold loading of 12.5 % appears to be necessary for a supported gold catalyst with small gold nanoparticles; although even higher loadings may be preferable for a higher power output in a fuel cell. Importantly, the insights gleaned from this study on the fundamental properties required for early activation, activity and stability of the gold catalysts could lead to a more intelligent design of gold-based catalysts in future.

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