Validity of the N\'{e}el-Arrhenius model for highly anisotropic Co_xFe_{3-x}O_4 nanoparticles

We report a systematic study on the structural and magnetic properties of Co_{x}Fe_{3-x}O_{4} magnetic nanoparticles with sizes between $5$ to $25$ nm, prepared by thermal decomposition of Fe(acac)_{3} and Co(acac)_{2}. The large magneto-crystalline anisotropy of the synthesized particles resulted in high blocking temperatures ($42$ K \leqq $T_B$ $\leqq 345$ K for $5 \leqq$ d $\leqq 13$ nm ) and large coercive fields ($H_C \approxeq 1600$ kA/m for $T = 5$ K). The smallest particles ($=5$ nm) revealed the existence of a magnetically hard, spin-disordered surface. The thermal dependence of static and dynamic magnetic properties of the whole series of samples could be explained within the N\'{e}el-Arrhenius relaxation framework without the need of ad-hoc corrections, by including the thermal dependence of the magnetocrystalline anisotropy constant $K_1(T)$ through the empirical Br\"{u}khatov-Kirensky relation. This approach provided $K_1(0)$ values very similar to the bulk material from either static or dynamic magnetic measurements, as well as realistic values for the response times ($\tau_0 \simeq 10^{-10}$ s). Deviations from the bulk anisotropy values found for the smallest particles could be qualitatively explained based on Zener\'{}s relation between $K_1(T)$ and M(T)

Cell death induced by the application of alternating magnetic fields to nanoparticle-loaded dendritic cells

In this work, the capability of primary, monocyte-derived dendritic cells (DCs) to uptake iron oxide magnetic nanoparticles (MNPs) is assessed and a strategy to induce selective cell death in these MNP-loaded DCs using external alternating magnetic fields (AMFs) is reported. No significant decrease in the cell viability of MNP-loaded DCs, compared to the control samples, was observed after five days of culture. The amount of MNPs incorporated into the cytoplasm was measured by magnetometry, which confirmed that 1 to 5 pg of the particles were uploaded per cell. The intracellular distribution of these MNPs, assessed by transmission electron microscopy, was found to be primarily inside the endosomic structures. These cells were then subjected to an AMF for 30 min, and the viability of the blank DCs (i.e., without MNPs), which were used as control samples, remained essentially unaffected. However, a remarkable decrease of viability from approximately 90% to 2-5% of DCs previously loaded with MNPs was observed after the same 30 min exposure to an AMF. The same results were obtained using MNPs having either positive (NH2+) or negative (COOH-) surface functional groups. In spite of the massive cell death induced by application of AMF to MNP-loaded DCs, the amount of incorporated magnetic particles did not raise the temperature of the cell culture. Clear morphological changes at the cell structure after magnetic field application were observed using scanning electron microscopy. Therefore, local damage produced by the MNPs could be the main mechanism for the selective cell death of MNP-loaded DCs under an AMF. Based on the ability of these cells to evade the reticuloendothelial system, these complexes combined with an AMF should be considered as a potentially powerful tool for tumour therapy.Comment: In Press. 33 pages, 11 figure

Application of magnetically induced hyperthermia on the model protozoan Crithidia fasciculata as a potential therapy against parasitic infections

Magnetic hyperthermia is currently an EU-approved clinical therapy against tumor cells that uses magnetic nanoparticles under a time varying magnetic field (TVMF). The same basic principle seems promising against trypanosomatids causing Chagas disease and sleeping sickness, since therapeutic drugs available display severe side effects and drug-resistant strains. However, no applications of this strategy against protozoan-induced diseases have been reported so far. In the present study, Crithidia fasciculata, a widely used model for therapeutic strategies against pathogenic trypanosomatids, was targeted with Fe_{3}O_{4} magnetic nanoparticles (MNPs) in order to remotely provoke cell death using TVMFs. The MNPs with average sizes of d approx. 30 nm were synthesized using a precipitation of FeSO_{4}4 in basic medium. The MNPs were added to Crithidia fasciculata choanomastigotes in exponential phase and incubated overnight. The amount of uploaded MNPs per cell was determined by magnetic measurements. Cell viability using the MTT colorimetric assay and flow cytometry showed that the MNPs were incorporated by the cells with no noticeable cell-toxicity effects. When a TVMF (f = 249 kHz, H = 13 kA/m) was applied to MNP-bearing cells, massive cell death was induced via a non-apoptotic mechanism. No effects were observed by applying a TVMF on control (without loaded MNPs) cells. No macroscopic rise in temperature was observed in the extracellular medium during the experiments. Scanning Electron Microscopy showed morphological changes after TVMF experiments. These data indicate (as a proof of principle) that intracellular hyperthermia is a suitable technology to induce the specific death of protozoan parasites bearing MNPs. These findings expand the possibilities for new therapeutic strategies that combat parasitic infections.Comment: 9 pages, four supplementary video file

The relevance of Brownian relaxation as power absorption mechanism in Magnetic Hyperthermia

The Linear Response Theory (LRT) is a widely accepted framework to analyze the power absorption of magnetic nanoparticles for magnetic fluid hyperthermia. Its validity is restricted to low applied fields and/or to highly anisotropic magnetic nanoparticles. Here, we present a systematic experimental analysis and numerical calculations of the specific power absorption for highly anisotropic cobalt ferrite (CoFe 2 O 4 ) magnetic nanoparticles with different average sizes and in different viscous media. The predominance of Brownian relaxation as the origin of the magnetic losses in these particles is established, and the changes of the Specific Power Absorption (SPA) with the viscosity of the carrier liquid are consistent with the LRT approximation. The impact of viscosity on SPA is relevant for the design of MNPs to heat the intracellular medium during in vitro and in vivo experiments. The combined numerical and experimental analyses presented here shed light on the underlying mechanisms that make highly anisotropic MNPs unsuitable for magnetic hyperthermia

Size dependence of the magnetic relaxation and specific power absorption in iron oxide nanoparticles

We report on the magnetic and power absorption properties of a series of iron oxide nanoparticles with average sizes ranging from 3 to 23 nm, prepared by thermal decomposition of Iron(III) acetylacetonate in organic media. From the careful characterization of the magnetic and physicochemical properties of these samples, we were able to reproduce the specific power absorption (SPA) values experimentally found, as well as their dependence with particle size, using a simple model of Brownian and Neel Relaxation at ´ room temperature. SPA experiments in ac magnetic fields (0 = 13 kA/m and f = 250 kHz) indicated that the magnetic and rheological properties played the fundamental rule to determine the heating efficiency at different conditions. A maximum SPA value of 344 W/g was obtained for a sample containing nanoparticles with = 12 nm and dispersion σ = 0.25. The observed SPA dependence with particle diameter and their magnetic parameters indicated that, for the size range and experimental conditions of f and H studied in this work, both Neel and Brown relaxation mechanisms are important to the heat generation observed.Fil: Lima, Enio Junior. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Torres, T. E.. Universidad de Zaragoza; EspañaFil: Rossi, L. M.. Universidade de Sao Paulo; BrasilFil: Rechenberg, R.. Universidade de Sao Paulo; BrasilFil: Berquo, T. S.. University Of Minnesota; Estados UnidosFil: Ibarra, A.. Universidad de Zaragoza; EspañaFil: Marquina, C.. Universidad de Zaragoza; EspañaFil: Ibarra, R. M.. Universidad de Zaragoza; EspañaFil: Goya, G. F.. Universidad de Zaragoza; Españ

Magnetic hyperthermia enhances cell toxicity with respect to exogenous heating

Magnetic hyperthermia is a new type of cancer treatment designed for overcoming resistance to chemotherapy during the treatment of solid, inaccessible human tumors. The main challenge of this technology is increasing the local tumoral temperature with minimal side effects on the surrounding healthy tissue. This work consists of an in vitro study that compared the effect of hyperthermia in response to the application of exogenous heating (EHT) sources with the corresponding effect produced by magnetic hyperthermia (MHT) at the same target temperatures. Human neuroblastoma SH-SY5Y cells were loaded with magnetic nanoparticles (MNPs) and packed into dense pellets to generate an environment that is crudely similar to that expected in solid micro-tumors, and the above-mentioned protocols were applied to these cells. These experiments showed that for the same target temperatures, MHT induces a decrease in cell viability that is larger than the corresponding EHT, up to a maximum difference of approximately 45% at T = 46 °C. An analysis of the data in terms of temperature efficiency demonstrated that MHT requires an average temperature that is 6 °C lower than that required with EHT to produce a similar cytotoxic effect. An analysis of electron microscopy images of the cells after the EHT and MHT treatments indicated that the enhanced effectiveness observed with MHT is associated with local cell destruction triggered by the magnetic nano-heaters. The present study is an essential step toward the development of innovative adjuvant anti-cancer therapies based on local hyperthermia treatments using magnetic particles as nano-heaters

Low-Dimensional Assemblies of Magnetic MnFe2O4 Nanoparticles and Direct In Vitro Measurements of Enhanced Heating Driven by Dipolar Interactions: Implications for Magnetic Hyperthermia

Magnetic fluid hyperthermia (MFH), the procedure of raising the temperature of tumor cells using magnetic nanoparticles (MNPs) as heating agents, has proven successful in treating some types of cancer. However, the low heating power generated under physiological conditions makes it necessary a high local concentration of MNPs at tumor sites. Here, we report how the in vitro heating power of magnetically soft MnFe2O4 nanoparticles can be enhanced by intracellular low-dimensional clusters through a strategy that includes: (a) the design of the MNPs to retain Neel magnetic relaxation in high-viscosity media, and (b) culturing MNP-loaded cells under magnetic fields to produce elongated intracellular agglomerates. Our direct in vitro measurements demonstrated that the specific loss power (SLP) of elongated agglomerates (SLP = 576 +/- 33 W/g) induced by culturing BV2 cells in situ under a dc magnetic field was increased by a factor of 2 compared to the SLP = 305 +/- 25 W/g measured in aggregates freely formed within cells. A numerical mean-field model that included dipolar interactions quantitatively reproduced the SLPs of these clusters both in phantoms and in vitro, suggesting that it captures the relevant mechanisms behind power losses under high-viscosity conditions. These results indicate that in situ assembling of MNPs into low-dimensional structures is a sound possible way to improve the heating performance in MFH

Magnetic properties and energy absorption of CoFe2O4 nanoparticles for magnetic hyperthermia

We have studied the magnetic and power absorption properties of three samples of CoFe2O4 nanoparticles with sizes from 5 to 12 nm prepared by thermal decomposition of Fe (acac)3 and Co(acac)2 at high temperatures. The blocking temperatures TB estimated from magnetization M(T) curves spanned the range 180 < TB < 320 K, reflecting the large magnetocrystalline anisotropy of these nanoparticles. Accordingly, high coercive fields HC \approx 1.4 - 1.7 T were observed at low temperatures. Specific Power Absorption (SPA) experiments carried out in ac magnetic fields indicated that, besides particle volume, the effective magnetic anisotropy is a key parameter determining the absorption efficiency. SPA values as high as 98 W/g were obtained for nanoparticles with average size of \approx12 nm.Comment: 4 pages, 3 figure