Blanco Andujar, C; (2014) Sodium carbonate mediated synthesis of iron oxide nanoparticles to improve magnetic hyperthermia efficiency and induce apoptosis. Doctoral thesis , UCL (University College London).

Abstract

Iron oxide nanoparticles are a popular choice for many current technologies, especially those with applications in biology and medicine. Novel syntheses that aim to improve their physicochemical properties, or adapt them to distinct practical applications, are constantly being reported. However, the reproducibility of these methods is not commonly studied, leading to promising products that have little chance of being commercially manufactured. Adherence to good manufacturing practice standards is a decisive factor in determining whether a material may be granted regulatory approval for industrial or clinical use. As such, tight control on the synthetic conditions is crucial to obtain consistent products. In this work initial experimentation was focused on the use of sodium carbonate―an environmentally friendly base―for the synthesis of iron oxide nanoparticles. Mild reaction conditions and slow kinetics allowed for the study of the reaction mechanism and led to controllable and reproducible results. However, functionalised suspensions could not be obtained due to the adsorption of carbonate onto the nanoparticle surface. A microwave reactor was then introduced to take advantage of the surface selective heating effect, aiding ligand exchange and enabling the production of nanoparticles with a range of surface functionalities. Their potential for magnetic hyperthermia, a promising therapeutic tool for the treatment of cancer, was investigated. Citric acid-iron oxide nanoparticles exhibited the highest heating performance, with an intrinsic loss power of 4.1 nHm2kg-1, which is 30% better than the best commercially available equivalent. Finally, their potential to treat near-surface or accessible tumours was tested in vitro on a human melanoma DX3 cell model. The results showed a controllable cell death via selective apoptosis or necrosis depending on the field and frequency applied. Time-lapse fluorescent microscopy experiments allowed the first direct observation of magnetic hyperthermia in adherent cells, where total-population cell death by apoptosis was observed.

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