Global vs. Local Heating in Magnetic Nanoparticle Hyperthermia

Resumo

Magnetic nanoparticles (MNPs) dissipate heat when subjected to an external alternating magnetic field. This heat released in the nanoscale has potential uses in a variety of techno- logical fields, ranging from catalysis to nanomedicine. This thesis deals with some not very studied aspects of magnetic nanoparticle hyperthermia (MNH), a new medical technique whose aim is to destroy cancer cells. This is achieved by introducing MNPs into the tumor and heating them by applying an alternating magnetic field. In 2013 MNH received the European regulatory approval for glioblastoma, the most common and aggressive brain tumor in humans and at the moment this technique is available in several German hospitals. However, despite this initial success and its huge potential, MNH has not yet attained a broad clinical application. The goal of this thesis is to investigate some features that are hampering the development of MNH and its translation into the clinics. It is commonly accepted that for MNH to be effective, the treatment area should achieve a uniform temperature around 43-45 ºC. Also, to maximize the heating output of the MNPs is considered a key priority in the MNH research field. This way, if MNPs heat more, the dose of magnetic material given to the patient can be decreased. And if tumor temperature reaches appropriate values and is distributed homogeneously, cancer tissue will be harmed without in- juring healthy cells. However, two aspects affect these generally agreed upon beliefs about MNH. Firstly, the temperature distribution in the tumor will not be uniform due to the fact that MNPs synthesis techniques cannot totally synthesize monodisperse MNPs both in shape and size. Therefore, each particle with different anisotropy K and volume V will release a differ- ent amount of energy E since E ∝ KV. This causes a distribution of local individual particle heating which may be responsible for undesired over- and infra-heating effects in cancer tissue. Besides being an indicator of the maximum attainable heat dissipation, anisotropy K plays a role in determining if the amplitude of the applied field will be able to make the MNPs release energy. In addition, there are some MNH experiments that report cell death without having a global macroscopic temperature variation. A possible explanation may be either mechanical damage or local heat. This second interpretation is supported by several experiments showing huge temperature gradients in the particle surface rapidly vanishing a few nanometers away. Therefore, this thesis studies variations in local heat caused by polydispersity in size and anisotropy, the link between local (individual particle level) and global (entire system) heat and how they affect the efficacy and safety of MNH. This is done by using a Metropolis Monte Carlo computational technique.