Glutathione-Enhanced Magnetic Hyperthermia

Abstract

Female breast cancer is the second most common cancer worldwide. A promising novel technique to treat early-stage breast cancer is the use of thermo-brachy therapy. This thesis analysed the effect of the cancer biomarker glutathione (GSH) on the magnetic hyperthermal effects of iron oxide nanoparticles. The synthesised nanoparticles with a diameter of 10±4 nm have been coated with cysteine and treated with hydrogen peroxide leading to their aggregation upon cross-linking. As the GSH concentration is higher around cancerous cells (10 μM instead of 3 μM), these nanoparticles would be more monodispersed as GSH could break the disulfide bonds between the cysteines. Since aggregated nanoparticles exhibit lower heating efficiencies, it was assumed that this method would allow for (partially) selective heating of the tumour. The addition of 10 μM GSH resulted in an 11% higher heating efficiency compared to 3 μM GSH when analysing the coated nanoparticles in an alternating magnetic field. However, a GSH concentration of 10 mM (intracellular GSH concentration in cancerous cells) gave a decrease in heating efficiency. Another methodology was proposed as well. Uncoated nanoparticles were encapsulated in a ZIF-8 framework. This framework is less stable in environments with a lower pH value and higher GSH concentration, which is the case in the tumour microenvironment. This methodology gave a 27% higher heating efficiency in a tumour-related GSH concentration and pH value. The differences with both the cysteine and ZIF-8-based methods are yet too small to limit thermal damage to healthy tissue. Modelling the diffusion and its influence on the temperature change, gave very local heating near the injection site due to slow diffusion. Therefore, while this thesis provided insights into the heating efficiencies in tumour-related conditions with both methodologies, addressing the current limitations can lead to significant advancements.