Understanding the benefits and limitations of magnetic nanoparticle heating for improved applications in cancer hyperthermia and biomaterial cryopreservation

Abstract

The current work focused on the ability of magnetic nanoparticles to produce heat in the presence of an applied alternating magnetic field. Magnetic nanoparticle hyperthermia applications utilize this behavior to treat cancer and this approach has received clinical approval in the European Union, but significant developments are necessary for this technology to have a chance for wider-spread acceptance.Here then we begin by investigating some of the important limitations of the current technology. By characterizing the ability of superparamagnetic and ferromagnetic nanoparticles to heat under a range of applied fields, we are able to determine the optimal field settings for clinical application and make recommendations on the highest impact strategies to increase heating. In addition, we apply these experimentally determined limits to heating in a series of heat transfer models, to demonstrate the therapeutic impact of nanoparticle concentration, target volume, and delivery strategy.Next, we attempt to address one of the key questions facing the field- what is the impact of biological aggregation on heating? Controlled aggregate populations are produced and characterized in ionic and protein solutions and their heating is compared with nanoparticles incubated in cellular suspensions. Through this investigation we are able to demonstrate that aggregation is responsible for up to a 50% decrease in heating. However, more importantly, we are able to demonstrate that the observed reductions in heating correlate with reductions in longitudinal relaxation (T1) measured by sweep imaging with Fourier transformation (SWIFT) magnetic resonance imaging (MRI), providing a potential platform to account for these aggregation effects and directly predict heating in a clinical setting.Finally, we present a new application for magnetic nanoparticle heating, in the thawing of cryopreserved biomaterials. A number of groups have demonstrated the ability to rapidly cool and preserve tissues in the vitreous state, but crystallization and cracking failures occur upon the subsequent thaw. Magnetic nanoparticles offer a potential solution to these issues, through their ability to provide rapid, uniform heating, and we illustrate this through heating in several cryoprotectant solutions and by modeling the effects of heating at the bulk and micro-scales.