Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.557163
Title: Lanthanide functionalised gold nanoparticles as MRI contrast agents
Author: Warsi, Muhammad F.
Awarding Body: University of York
Current Institution: University of York
Date of Award: 2010
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Abstract:
The aim of this Ph. D. project was to synthesize and characterise nanoparticle-based MRI contrast agents. In the first instance, the DTPA (diethylenetriaminepentaacetic acid) based ligand was designed, synthesized and characterised. This ligand was utilised for stabilisation of gold nanoparticles. The gold nanoparticles protected by DTPA based ligand were characterised using UV-Vis, NMR spectroscopies, TGA and TEM. The nanoparticles were then loaded with gadolinium. The relaxivity of gadolinium loaded gold nanoparticles were studied using inversion recovery method and compared with commercially available MRI contrast agents (i.e. Gd-DTPA). The Gd-loaded AuNPs showed only a moderate increase in their relaxivity as compared to the Gd-DTPA complex. The factors limiting the relaxivity of Gd-loaded AuNPs were explored using EPR spectroscopy. For EPR measurements, Gd3+ was replaced with vanadyl (VO2+) which gives EPR spectra sensitive to the rate of molecular tumbling on nanosecond time scale. The EPR measurements of VO2+-loaded AuNPs showed that the nanoparticle attached metal ion retains high molecular mobility. This is likely responsible for only a moderate increase in relaxivity. We next explored different strategies for increasing the relaxivity of gold nanoparticles based MRI contrast agents. In the first strategy, in order to enhance ligand packing at AuNPs surface, the size of the AuNPs was increased from ~2.0 nm to ~6.0 nm. The relaxivity was found to increase with the increased size of the AuNPs. Secondly, polyelectrolyte coating of charged Gd-loaded AuNPs surface also resulted in increase of relaxivity due to better immobilisation of the Gd3+ ions. Gold nanoparticles were also used as templates for nitroxide based redox sensitive MRI contrast agents. The reducing behaviour and relaxivity of nitroxide protected AuNPs was measured and found slightly better than that of free nitroxide. Finally other useful applications of nanoparticles protected by DTPA based ligand were explored. For example, the DTPA ligand can also chelate strongly with other lanthanides such as Eu3+, Tb3+etc. The luminescence measurements of lanthanides (Eu3+ and Tb3+) loaded onto AuNPs were explored. Lanthanide-loaded AuNPs were also used as model compounds to test an important EPR methodology after labelling with a nitroxide based spin label.
Supervisor: Chechik, Victor Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.557163  DOI: Not available
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