Nanoscale thermal phenomena in the vicinity of magnetic nanoparticles in alternating magnetic fields

Abstract

Magnetic nanoparticles can be made to dissipate heat to their immediate surroundings in response to an applied alternating magnetic field. This property, combined with the biocompatibility of iron oxide nanoparticles and the ability of magnetic fields to penetrate deep in the body, makes magnetic nanoparticles attractive in a range of biomedical applications where thermal energy is used either directly to achieve a therapeutic effect or indirectly to actuate the release of a therapeutic agent. Although the concept of bulk heating of fluids and tissues using energy dissipated by magnetic nanoparticles has been well accepted and applied for several decades, many new and exciting biomedical applications of magnetic nanoparticles take advantage of heat effects that are confined to the immediate nanoscale vicinity of the nanoparticles. Until recently the existence of these nanoscale thermal phenomena had remained controversial. In this short review we summarize some of the recent developments in this field and emerging applications for nanoscale thermal phenomena in the vicinity of magnetic nanoparticles in alternating magnetic fields.

Keywords: hyperthermia; iron oxide; local heating; magnetic nanoparticle; magnetically triggered drug release.

Figure 1

In magnetic fluid hyperthermia (MFH), magnetic nanoparticles dissipate heat in the presence of an alternating magnetic field (AMF). The particles are delivered to cancer tissues and cells, and can be used to achieve locoregional hyperthermia upon application of an AMF to the targeted region.

Figure 2

Estimated tissue iron oxide concentrations required to eradicate a spherical tumor as a function of tumor volume by hyperthermia (MFH, solid lines) or by intracellular heating (MagMED, dashed lines). MFH calculations are based on the solution of Penne’s bioheat equation, achieving a surface tumor temperature of 45°C, and reported values of the specific absorption rate (SAR) of magnetic nanoparticles. Intracellular heating calculations assume a thermal dose of 18 μJ/cell required, over 2 hr of AMF application, and a cancer cell density of 5×10⁷ cells/cm³. The green shaded region corresponds to the range of MNP accumulation that seems potentially feasible without magnetic targeting, and the blue shaded region corresponds to the range of MNP accumulation that seems potentially feasible with magnetic targeting, based on recent reports.^[28]

Figure 3

Observations of local heating in the vicinity of magnetic nanoparticles when an AMF (8.4 G, 40 MHz) is applied. The surface of the magnetic nanoparticles was functionalized with DyLight fluorophore, whereas yellow fluorescent protein (YFP) was present in the surrounding fluid. Reproduced with permission.^[30] Copyright 2013, Nature Publishing Group.

Figure 4

Iron oxide magnetic nanoparticles coated with a thermoresponsive-fluorescent polymer consisting of a copolymer of benzofuranzan and N-isopropylacrylamide experience nanoscale heating upon application of an AMF (38.4 kA/m, 233 kHz). The fluorescence of the benzofuranzan dye increases with change in environment polarity, which changes with temperature due to the thermoresponsive properties of pNIPAM. With external heating the fluorescence is observed to increase at a temperature of ~40 °C, whereas upon application of an AMF the fluorescence is observed to increase even though the bulk temperature is 20 °C. Reproduced with permission.^[31] Copyright 2013, Nature Publishing Group.

Figure 5

Change in temperature as a function of different applied magnetic field amplitudes and PEG spacer molecular weight, as determined from the rate of release of a dye conjugated to magnetic nanoparticles through a thermally labile crosslinker. Reproduced with permission.^[32] Copyright 2013, American Chemical Society.

Figure 6

Clonogenic surviving fraction as a function of specific absorption rate for cancer cells (MDA-MB-468) exposed to iron oxide (IO) magnetic nanoparticles without/with the peptide epidermal growth factor (EGF). Unbound/uninternalized nanoparticles were removed prior to field application and the temperature remained constant at 37°C during field application. Increasing SAR has a slight effect on clonogenic survival of cells treated with the non-targeted particles (Field IO), but has a significant effect on clonogenic survival of cells treated with targeted nanoparticles (Field IO-EGF). Reproduced with permission.^[37] Copyright 2011, American Chemical Society.

Figure 7

Magnetically-mediated activation of lysosomal death pathways through intracellular energy delivery by magnetic nanoparticles.