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Title: Non-ferrous metal doped magnetosomes : growing enhanced magnetic nanoparticles in vivo for biomedical applications
Author: Alhursh, Zainab
ISNI:       0000 0004 7964 5695
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2019
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Cancer is a major disease, affecting people globally. Breast cancer specifically, is one of the primary types of cancer affecting women between the ages of 50 and 70. Many treatments have been developed for this disease, but for certain types of tumour, current treatments are failing. Therefore, there is an urgent need for new treatments. An example of a new type of treatment is the use of magnetic nanoparticles. These particles are nanoscale crystals of iron oxide such as magnetite. They can be magnetically driven to specific targets in vivo using a magnetic field external to the body. Drug molecules can be attached to them for magnetic drug delivery at lower doses. The particles can generate heat when an alternating magnetic field is present. This is known as magnetic hyperthermia, and it is capable of killing tumour cells. The particles can also be used in MRIs for cancer diagnosis. For these applications, the particles must have a narrow size distribution, high purity, be biocompatible and stable, and have specific magnetic properties. Achieving all of these requirements is difficult using synthetic methods. However, magnetotactic bacteria use biomineralisation to produce precise size and shape particles of magnetite, which are known as magnetosomes. This study aimed to test and enhance the leading magnetosomes for cancer treatment. Magnetosomes were synthesized with varying concentrations of Mn2+, Co2+ and Cu2+ in order to optimise their magnetic properties for magnetic hyperthermia in cancer cell lines, where Co-doped magnetosomes displayed the highest coercivity (420 Oe) compared to native magnetosomes (125 Oe). This cobalt doping produced the highest apoptotic cell death in vitro (26.4%) and following the in vivo, testing confirmed that the presence of special magnetosomes with Co-doped magnetosomes within a tumour caused cell death around the sites of magnetosome localisation, compared to areas where there are no magnetosomes. In addition, for their MRI response, Mn doping enhances the T2 relaxation with increasing concentration of manganese, whereas in native magnetosomes, the Mn doping showed the highest saturation magnetisation of Ms 112 emug-1 and the highest value of relaxivity 434 mM-1S-1, which indicates the high degree of sensitivity in MRI. Furthermore functionalising the magnetosome surface with streptavidin has confirmed cell uptake by fluorescence microscopy and flow cytometry for some future applications with bioactive substances. The cell uptake was highest at 0.18 mg/ml concentration with low toxicity, as evidenced by the flow cytometry, MTT, and Endotoxin assays. The outcome of this work is optimised concentrations of magnetosomes for cell uptake and cytotoxicity. The magnetic properties of magnetosomes have been enhanced through Co2+ and Mn2+ doping, and cell uptake has been investigated using TEM and fluorescence microscopy of functionalised magnetosomes. The more promising magnetosomes for magnetic hyperthermia have been tested in tumours in mice.
Supervisor: Staniland, Sarah Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available