Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.564261
Title: Multifunctional magnetic nanoparticles for biomedical applications
Author: Olariu, Cristina
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2012
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Abstract:
The objective of this thesis was to develop and prepare multifunctional magnetic nanoparticles with targeting and bimodal imaging capabilities for cancer diagnostic applications. Superparamagnetic iron oxide nanoparticles (SPIONs) were the key component in the multifunctional nanoparticles prepared. In a first approach, alkoxysilane ligands were used to introduce functional groups such as amino, bromo, iodo, nitrile, and vinyl on the surface of SPIONs. Physicochemical analyses showed that each silane ligand formed a dense silane monolayer covalently attached to the nanoparticle surface. The amino-functionalised SPIONs were successfully modified yielding amino and carboxylic acid-bifunctionalised SPIONs using a succinylation reaction. This nanoparticle system showed no cytotoxicity during cell viability evaluations. Further conjugation with fluorescent dye and antibodies produced targeted bimodal optical/magnetic resonance imaging (MRI) agents, confirmed by good contrast enhancement capabilities. The conjugated antibody successfully enabled the targeted delivery of SPIONs to pancreatic cancer cells in vitro. The targeting efficiency and the nanoparticle cellular uptake were monitored using fluorescence and confocal microscopy. In a second approach, hydrophobic and monodisperse SPIONs were coated with amphiphilic polyoxazoline to produce colloidally stable magneto-micelles. This magneto-micellar system showed high colloidal stability in water, phosphate buffered saline as well as at different pH values. Fluorescent dyes were successfully co-assembled into the magneto-micelles providing for the localisation of the nanoparticles in the cells by confocal microscopy. Antibodies conjugated to nontoxic magneto-micelles allowed for binding to specific receptors present on pancreatic cancer cells. The targeting efficiency and accumulation of the antibody labelled magneto-micelles into pancreatic cancer cells was evaluated using live cell confocal microscopy. Their performance as MRI contrast agents was evaluated using relaxivity measurements and it was shown that the clustering effect of the SPIONs within the core of the micelle is particularly favourable for enhancing the contrast on MRI images. Both approaches provided efficient routes of preparation of multifunctional platforms to achieve the desired targeting and bimodal imaging capabilities.
Supervisor: Rosseinsky, M. J.; Claridge, J. B. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.564261  DOI: Not available
Keywords: Q Science (General) ; QD Chemistry
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