thesis

Magnetite/silica core-shell nanoparticles for HER-2 targeted magnetic resonance imaging of breast tumours.

Abstract

Contrast agents allow for greater detail of specific internal structures to be obtained under clinical MR imaging. These images are used to aid in the diagnosis of conditions or damage including tumours and other cancerous tissues. Gadolinium has for quite a while been used as a primary material for this purpose but increasing concerns regarding toxicity are adding pressure to seek alternate materials. Magnetite offers many properties that would make it an excellent contrast material and several products have come to market but are restricted in their application primarily due to particle size. This thesis aims to approach the problems associated with magnetite nanoparticles and their use in intravenous systems. This requires reducing the overall particle size and ensuring biocompatibility. This was accomplished by modifying the core particle size by altering the thermal decomposition parameters and surface coating the material with a layer of silica. A preliminary investigation was made using quasi cubic magnetite particles to investigate the biocompatibility and performance as an MR contrast agent. Based on these findings a second core shell nanoparticle system was formed using modified techniques to reduce the overall particle size by shrinking the core magnetite and the silica shell thickness. These particles were subsequently surface modified with Herceptin® to facilitate the selective uptake of the particles into specific cancerous 12 cells. The particles were examined for their biocompatibility, structural stability and selective uptake into SKBR3 cells in vitro and in vivo in live breast tumour baring mice. All the studies were undertaken in MRI scanners in use by clinicians at the Peter MacCallum Cancer Research Centre. This demonstrated that in a clinical setting, these core shell particles can be made to selectively target specific tumours in significant number to cause notable localised contrast at the target site

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