Radiotherapy is currently employed in the treatment of 50% of cancer patients. Cancer's heterogeneous nature mean optimal use of radiotherapy will be through combination and targeted therapies. Studies investigating the radiosensitising potential of solid gold nanoparticles have reported successful radiosensitisation only in combination with low kV radiation sources, but not with high kV or MV radiation. HGNs have been employed in photothermal ablation therapy, little work has been performed to investigate their potential as radiosensitisers, despite the superior physical properties, compared to solid AuNPs. The aims of this study were to investigate the radiosensitising potential of solid AuNPs and HGNs in combination with kV external beam radiation (XBR) and high kV β and γ radiation from ¹³¹I, from [¹³¹I]-MIBG. The study then aimed to investigate the effect of solid gold nanoparticles (AuNPs), hollow gold nanoparticles (HGNs), XBR and [¹³¹I]-MIBG alone and in combination on the growth of 3D MTS models. Radiosensitisation was measured by a decrease in clonogenic cell survival and quantified using the linear quadratic model. Association of radiosensitisation with changes in the cell cycle, dynamics of DNA double strand break (DSB) formation and repair and apoptotic cell death was assessed. The growth of spheroids was examined by assessing changes in spheroid volume. Significant radiosensitisation was observed in UVW/NAT and SK-N-BE cells, when solid AuNPs and HGNs were combined with [¹³¹I]-MIBG which was associated with an increase in DNA DSB formation. Solid AuNPs in combination with XBR induced minimal radiosensitisation, compared to significant radiosensitisation observed with HGNs. Solid AuNPs and HGNs alone and in combination with XBR and [¹³¹I]-MIBG had no significant effect on the growth of multicellular tumour spheroids (MTS), whereas exposure to XBR and [¹³¹I]-MIBG induced a dose dependant decrease in spheroid growth.
|Date of Award||29 Apr 2016|
- University Of Strathclyde
|Sponsors||University of Strathclyde & BBSRC (Biotech & Biological Sciences Research Council)|
|Supervisor||Marie Boyd (Supervisor) & Oliver Brook Sutcliffe (Supervisor)|