Current cancer therapies are highly cytotoxic and their delivery to exclusively the affected site is poorly controlled, resulting in unavoidable and often severe side effects. In an effort to overcome such issues, magnetic nanoparticles have been recently gaining relevance in the areas of biomedical applications and therapeutics, opening pathways to alternative methods. This led to the concept of magnetic particle hyperthermia in which magnetic nano beads are heated by a high power magnetic field. The increase in temperature kills the cancer cells, which are more susceptible to heat in comparison to healthy cells. In this dissertation, the possibility to kill cancer cells with magnetic nanowires is evaluated. The idea is to exploit a magnetomechanical effect, where nanowires cause cancer cell death through vibrating in a low power magnetic field. Specifically, the magnetic nanowires effects to cells in culture and their ability to induce cancer cell death, when combined with an alternating magnetic field, was investigated. Nickel and iron nanowires of 35 nm diameter and 1 to 5 μm long were synthesized by electrodeposition into nanoporous alumina templates, which were prepared using a two-step anodization process on highly pure aluminum substrates. For the cytotoxicity studies, the nanowires were added to cancer cells in culture, varying the incubation time and the concentration. The cell-nanowire interaction was thoroughly studied at the cellular level (mitochondrial metabolic activity, cell membrane integrity and, apoptosis/necrosis assay), and optical level (transmission electron and confocal microscopy). Furthermore, to investigate their therapeutic potential, an alternating magnetic field was applied varying its intensity and frequency. After the magnetic field application, cells health was measured at the mitochondrial activity level. Cytotoxicity results shed light onto the cellular tolerance to the nanowires, which helped in establishing the appropriate nanowire concentrations to use the nanowires + alternating magnetic field combination as a cancer treatment. Different levels of cancer cell death were achieved by changing the incubation time of the nanowires with the cells and the alternating magnetic field parameters. Cell viability was significantly affected in terms of mitochondrial activity and cell membrane integrity after applying the treatment (nanowires + alternating magnetic field) using a low-frequency alternating magnetic. Theoretical calculations considering the magnetic and viscous torques showed that the nanowires vibrate as a consequence of the applied magnetic field. This, alongside the fact that no temperature increase was measured during the treatment, makes the magnetomechanical effect the most probable action mechanism in the applied treatment that is inducing cell death. Inducing cancer cell death via magnetomechanical action using magnetic nanowires resulted in killing up to 60% of cancer cells with only 10 minutes of treatment. The required magnetic field for treatment is in a low power regime, which is safe, does not cause any discomfort to the patients, and can be generated with compact and cheap instruments.
|Date made available
|KAUST Research Repository