Synthesis and Process Optimization of Multicore Iron Oxide Nanoparticles as Responsive Components for Biomedical Applications

Iron oxide magnetic nanoparticles (MNPs) have been considered since the 1970s as key in the development of smart responsive materials, with benefits that makes them interesting in a wide range of biomedical applications such as magnetic hyperthermia, MRI contrast agents’ enhancement, target drug delivery systems and could potentially be essential for cancer treatments. Iron oxide MNPs have become one of the main areas of research in the line of nanobiotechnology due to their biocompatibility, low biotoxicity, unique magnetic properties and biodegradability. Moreover, these can be fine-tuned in size and shape to tailor them to specific biomedical needs. The magnetic material used in this project are multicore maghemite (γ-Fe2O3) MNPs or nanoflowers due to their high heating efficiency in suspension on application of an AC field. This characteristic is of paramount importance in applications such as magnetic field induced localised heating for tumour cauterisation, making magnetic nanoflowers (MNFs) a very interesting type of MNPs. High specific absorption rates (SAR) values recorded of 300 ± 10 W/g allow them to be used for magnetic hyperthermia or targeted drug release at low concentrations while retaining their high heating efficiency and thus further reducing any possibility of biotoxicity. MNF properties can be improved using magnetic separation as a post-purification process that provides particle fractions with different magnetocrystalline properties from the one batch. This technique is called Magnetic Field Flow Fractionation (MFFF); an MFFF device was developed recently in the Brougham group and was developed in the first part of this project to obtain fractions from both bare and PEGylated MNFs suspensions, which do have very distinct magnetic properties and in some cases sizes. The use of this device has demonstrated that size monodisperse suspensions have distributions of magnetic properties. Hence the instrument is an interesting and effective tool for assessing both size and magnetic distribution of MNPs in suspension. The second part of this project revolves around MNF synthesis optimisation to provide a more robust protocol that could yield suspensions with higher heating efficiencies. Synthesis optimisation has been a focus in the Brougham group, where different parameters such as NaOH equivalents, heating ramp, reaction time, variable oxidant amount have been optimised to maximise SAR values and provide that SAR reproducibly. In this part of the project, the water content in the reaction will be studied, as it is known to play a critical role in the formation of MNFs through mechanisms that are not yet fully understood in the literature. Through solvent dehydration (i.e. DEG and NMDEA) and manually adding controlled volumes of water different for each synthesis, a study on SAR optimisation was carried out. Two different methods were used to add the water in the system, which yielded distinct trendlines and results on the heating efficiency and morphology found in those suspensions.