Magnetic Nanoparticle Hyperthermia

Abstract

The synergic exploitation of electromagnetic fields and nano-components has led, in the last two decades, to the definition of new therapeutic tools for the treatment of cancer. One of these tools is the Magnetic Nanoparticle Hyperthermia, an emerging hyperthermic treatment where the tumor heating is achieved by accumulating into it magnetic nanoparticles and applying a low frequency magnetic field. Magnetic Nanoparticle Hyperthermia is very attractive thanks to the biocompatibility and low toxicity of the employed magnetic nanoparticles and the possibility of their selective accumulation into the tumor by means of minimally invasive administration routes. Moreover, they exhibit high dissipation capability and the transparency of the human tissues to low frequency magnetic fields allows treating tumors deeply located in the body. For these reasons, Magnetic Nanoparticle Hyperthermia has been extensively investigated, and clinical trials on human patients have been performed since 2003, with encouraging results and reduced side effects, especially concerning brain tumors. In this framework, an important topic is the characterization, both theoretical and experimental, of the properties, particularly the losses, of magnetic nanoparticles. The aim is to identify the nanoparticle parameters (size and shape) and the exposure conditions (magnetic field amplitude and frequency) that maximize the dissipation capability of the magnetic nanoparticles, in order to minimize their concentration in the tumor. However, maximizing the magnetic losses is only one face of the coin: one must also avoid overheating of the healthy tissue surrounding the tumor, due to the eddy currents induced by the applied field. Therefore, one should actually face a more complex constrained optimization problem. This explains in part why the setting of the operative parameters is still based on empirical, possibly over-restrictive, criteria, although the individuation of the actual optimal working conditions is a key point to extend its clinical effectiveness. In this chapter we will prevalently address this last aspect of Magnetic Nanoparticle Hyperthermia. We will begin with an overview of the main biological and physiological effects that are at the basis of the use of heating as an oncological treatment and of the main hyperthermia modalities. Next, we will introduce and discuss Magnetic Nanoparticle Hyperthermia, reporting the main results of its feasibility assessment and of the clinical trials performed up to now. Then, after revising the state of the art and current issues concerning the optimization of the magnetic nanoparticle losses, we will present a recently proposed criterion for the optimal choice of the working conditions in Magnetic Nanoparticle Hyperthermia, critically discussing the reliability of the analytical models on which it is based. Numerical results relative to the challenging and clinically relevant case of brain tumors, obtained by exploiting a 3D realistic model of the human head, will be presented, discussing their significance and practical relevance. Then, exploiting these results, the limits of clinical applicability of Magnetic Nanoparticle Hyperthermia for the treatment of brain tumors in adult patients will be estimated. A discussion on the possible future developments will conclude the chapter.