Learning from nature to improve the heat generation of iron-oxide nanoparticles for magnetic hyperthermia applications

Abstract

The performance of magnetic nanoparticles is intimately entwined with their structure, mean size and magnetic anisotropy. Besides, ensembles offer a unique way of engineering the magnetic response by modifying the strength of the dipolar interactions between particles. Here we report on an experimental and theoretical analysis of magnetic hyperthermia, a rapidly developing technique in medical research and oncology. Experimentally, we demonstrate that single-domain cubic iron oxide particles resembling bacterial magnetosomes have superior magnetic heating efficiency compared to spherical particles of similar sizes. Monte Carlo simulations at the atomic level corroborate the larger anisotropy of the cubic particles in comparison with the spherical ones, thus evidencing the beneficial role of surface anisotropy in the improved heating power. Moreover we establish a quantitative link between the particle assembling, the interactions and the heating properties. This knowledge opens new perspectives for improved hyperthermia, an alternative to conventional cancer therapies.

Figure 1. TEM images.

Iron-oxide nanocubes (a) with average edge length of 20 ± 4 nm; inset reveals 2D self-assembly arrangements. (b) Corresponding TEM micrograph of 40 nm nanocubes. As can be seen in the larger area view, the particles organize themselves in different chain-like configurations. (c) High-resolution observation of crystal structure revealing (222) fringes of the inverse spinel iron oxide. Inset exhibits the FFT spectrum.

Figure 2. Tomography.

3D reconstruction of cuboctahedral shape particles, from images obtained at different tilt angles relative to the electron beam, after 40 iterations (see Methods). (a) Nanocube cluster. Neighboring nanocubes have {100} surfaces face to face separated by a distance above 2 nm due to hydrocarbon ligands. (b) Single nanocube in its original context. (c) Illustration of small deviations from perfect cubic symmetry.

Figure 3. SQUID.

(a) Magnetic hysteresis loops recorded at 300 K for 20 nm and 40 nm square nanoparticles. Inset shows the low field region of the hysteresis loop. (b) Magnetic hysteresis loops recorded at 5 K.

Figure 4. Hyperthermia.

Specific Absorption Rate (SAR) for (a) 40 nm and (b) 20 nm iron oxide nanocubes extrapolated from experimental thermal response curves at different maximum applied magnetic fields (Figure S7 within the Supplementary Information). Data are expressed as the mean of 3 measurements ± the standard error of the mean. Inset shows suspension stability after measurement.

Figure 5. Comparison of Experimental and Computational Results.

SAR values for two nanoparticle solutions of similar concentration (0.5 mg/mL) and size volume but different shape indicating enhancement of SAR values for the 20 nm square nanoparticles. (a) Experimental results. (b) MC simulations for the macrospin model with dipolar interactions at 300K.

Figure 6. Magnetization simulation.

Hysteresis loops for a spherical (red circles, diameter 20 nm) and a cubic particle (blue squares, side 20 nm) obtained from MC simulations of an atomistic spin model of maghemite at low temperature. In both, uniaxial anisotropy at the core and Néel surface anisotropy have been considered. Snapshots show the spin configurations in the remanent state. Spins have been colored according to their projection into the magnetic field direction (z axis) from red (+1) to blue (−1).

Figure 7. Chain-like assemblies.

Computed hysteresis loops for arrays of nanoparticles of different length (values of N indicated), and the limit case of a single particle, where H_A = 2 K/M_S is the anisotropy field of the particles. The temperature was introduced in terms of the anisotropy energy barrier of the particles, t = k_BT/2KV = 0.001. The inset shows the magnetic response on increasing the temperature for the N = 1 and 10 cases, illustrating the higher thermal stability of the chains. The schematic picture shows particles within a chain possessing easy axes contained within an angle of π/4 (cubes are only for illustration purposes, since spherical nanoparticles could also form chains).