| Summary: | An estimated 12 million people worldwide are diagnosed with cancer every year, with around 17 million cancer-related deaths per year predicted by 2030 (Thun et al. 2010). Contemporary clinical treatments include surgery, chemotherapy and radiotherapy, however all vary in success and exhibit unpleasant side effects. Localised tumour hyperthermia is a moderately new cancer treatment envisaged by researchers, which exploits exclusive tumour vulnerabilities to specific temperature profiles (42-45°C) leading to cancer cell apoptosis, whilst normal tissue cells are relatively unaffected. Hyperthermia is therefore proposed as an alternative potential therapy for cancer, by delivering localised treatment to cancer cells, without the severe side effects associated with traditional therapies. This project aimed to investigate potential hyperthermic treatment of cancer cells in vitro by adopting nanomedicine principles. Inorganic nanoparticles, such as gold or iron oxide, are both capable of generating heat when appropriately stimulated, therefore both have been suggested as candidates for inducing localised tumour heating following their internalisation into cells. In this project, both gold (GNPs) and magnetic (mNPs) were individually assessed for their potential to deliver toxic thermal energy to bone cancer cells (MG63) and breast cancer cells (MCF-7). Studies were carried out both in standard 2D monolayer and in 3D tumour spheroids. When considering use in vivo, it is essential that both GNPs and mNPs are biocompatible, therefore initial studies characterised the cell viability and metabolic activity following incubation with the NPs. The NP internalisation was subsequently verified, prior to hyperthermic studies. Following hyperthermic treatment, both GNPs and mNPs were confirmed as inducing cancer cell death. Further studies were carried out using the GNPs, to identify the cell death pathways activated, where mitochondrial stress was evident following 2D culture tests. Gene and protein expression analysis indicated that cell death occurred predominantly via several apoptotic pathways, through increased fold expression changes in apoptotic markers. Interestingly, cell protective mechanisms were simultaneously switched on, as cells were also observed to exhibit thermotolerance with a number of heat shock proteins (Hsps) being substantially increased during hyperthermic treatments.
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