Gold-iron nanowires for magneto-mechanical and radiation therapy of glioblastoma multiforme
File(s)
Author(s)
Taylor, Jonathan
Type
Thesis
Abstract
Glioblastoma multiforme (GBM) is an aggressive type of brain tumour which urgently requires additional therapeutic options. Patients typically survive just 15 months (1) under the current standard of care and innovations like magneto-thermal therapy and tumour-treating electric fields have as-yet failed to extend this survival time by more than a few months. Nanomedicine has long promised to harness novel physical effects for innovative therapies such as enhanced radiotherapy (2), magneto-thermal therapy (3) and photothermal therapy (4). Following decades of research, this technology is beginning to be clinically applied. In this work, gold-iron nanowires are tested for magneto-mechanical therapy and enhanced radiotherapy of GBM. The rationale is that magnetic iron-containing nanowires mechanically rotate inducing cellular damage and the gold scatters x-rays due to its high atomic number, enhancing the local radiotherapy dose. Synthesis of gold-iron nanowires is achieved using a hard-template electrochemical method, controlling the material composition by tuning the deposition current. The nanowire deposits were characterised for their crystallographic and magnetic properties showing they are polycrystalline and have saturation magnetisations of 120 emu/g (low gold nanowires) 90emy/g (high gold nanowires). Computational modelling was used to show the nanowires respond to both alternating and rotating magnetic fields and to quantify the optimal frequencies for magneto-mechanical therapy. For a 0.76mT uniform alternating field, the optimal/maximal frequency for the nanowires was determined to be ~100Hz in water and ~1Hz in the cells, assuming a cytoplasm viscosity of 68mPas. Subsequent in vitro testing using an MTS cell-metabolism assay demonstrated that applying magneto-mechanical therapy alongside radiotherapy resulted in a synergistic effect, reducing cell viability significantly to 39±2%. The increased efficacy of radiotherapy post-magneto mechanical therapy was attributed to the higher loading of the particles in the cells following application of the magnetic field. Membrane disruption was observed using high-resolution scattering-type scanning near field optical microscopy (s-SNOM) bioimaging. In summary, this proof-of-concept in vitro study demonstrates the potential of combining magneto-mechanical therapy and radiosensitisation, laying the foundation for further clinical development of gold-iron nanowires for treatment of GBM.
Version
Open Access
Date Issued
2022-08
Date Awarded
2023-03
Copyright Statement
Creative Commons Attribution NonCommercial Licence
License URL
Advisor
Porter, Alexandra
Ryan, Mary
Williams, Matthew
Publisher Department
Materials
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)