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

Superparamagnetic relaxation in Cu_{x}Fe_{3-x}O_{4} (x=0.5 and x=1) nanoparticles

The scope of this article is to report very detailed results of the measurements of magnetic relaxation phenomena in the new Cu$_{0.5}$Fe$_{2.5}$O$_{4}$ nanoparticles and known CuFe$_{2}$O$_{4}$ nanoparticles. The size of synthesized particles is (6.5$\pm$1.5)nm. Both samples show the superparamagnetic behaviour, with the well-defined phenomena of blocking of magnetic moment. This includes the splitting of zero-field-cooled and field-cooled magnetic moment curves, dynamical hysteresis, slow quasi-logarithmic relaxation of magnetic moment below blocking temperature. The scaling of the magnetic moment relaxation data at different temperatures confirms the applicability of the simple thermal relaxation model. The two copper-ferrites with similar structures show significantly different magnetic anisotropy density and other magnetic properties. Investigated systems exhibit the consistency of all obtained results.Comment: 18 pages, 8 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

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)

Numerical Simulation of Magnetic Interactions in Polycrystalline YFeO3

The magnetic behavior of polycrystalline yttrium orthoferrite was studied from the experimental and theoretical points of view. Magnetization measurements up to 170 kOe were carried out on a single-phase YFeO3 sample synthesized from heterobimetallic alkoxides. The complex interplay between weak-ferromagnetic and antiferromagnetic interactions, observed in the experimental M(H) curves, was successfully simulated by locally minimizing the magnetic energy of two interacting Fe sublattices. The resulting values of exchange field (H_E = 5590 kOe), anisotropy field (H_A = 0.5 kOe) and Dzyaloshinsky-Moriya antisymmetric field (H_D = 149 kOe) are in good agreement with previous reports on this system.Comment: 26 pages, 9 figure

Spin Disorder and Magnetic Anisotropy in Fe3O4 Nanoparticles

We have studied the magnetic behavior of dextran-coated magnetite (Fe$_3$O$_4$) nanoparticles with median particle size \left=8 $nm$. Magnetization curves and in-field M\"ossbauer spectroscopy measurements showed that the magnetic moment $M_S$ of the particles was much smaller than the bulk material. However, we found no evidence of magnetic irreversibility or non-saturating behavior at high fields, usually associated to spin canting. The values of magnetic anisotropy $K_{eff}$ from different techniques indicate that surface or shape contributions are negligible. It is proposed that these particles have bulk-like ferrimagnetic structure with ordered A and B sublattices, but nearly compensated magnetic moments. The dependence of the blocking temperature with frequency and applied fields, $T_B(H,\omega)$, suggests that the observed non-monotonic behavior is governed by the strength of interparticle interactions.Comment: 11 pages, 7 figures, 3 Table

Role of anisotropy, frequency, and interactions in magnetic hyperthermia applications: noninteracting nanoparticles and linear chain arrangements

Efforts by numerous research groups have provided a deeper insight into the physical mechanisms behind the power absorption of single-domain magnetic nanoparticles in magnetic-fluid-hyperthermia applications and theoretical models now account for the main experimental observations. However, the role of all parameters relevant to the magnetic relaxation remains a matter of debate. Here, we employ a nonlinear model for the magnetic relaxation of single-domain magnetic nanoparticles with uniaxial effective anisotropy and evaluate the influence of particle-intrinsic parameters as well as experimental conditions on the power absorption of both noninteracting and interacting systems (linear arrangements). These effects are assessed through the enclosed hysteresis area of the magnetization loops as a function of relative anisotropy hK (the anisotropy field with respect to the amplitude of the ac field), i.e., the "area curve"of the system. These curves can be divided into four regions with distinct magnetic responses and boundaries that depend on the particle size, frequency of the applied field and interactions. Interactions change the effective anisotropy of the system and shift the area curve towards lower hK values. For the low relative anisotropy range, dipolar interactions increase the area of the hysteresis loops [thus, the specific power absorption (SPA)], while they are detrimental or produce nonsignificant effects for the range of high relative anisotropy. Our study resolves seemingly contradictory results of interaction effects in linear arrangements recently reported in the literature. Simulations of randomly oriented particles and chains were contrasted with the oriented cases. An analytical approach and the thermal interpretation of its validity range are discussed, both aimed at the design of nanoparticles and the choice of the experimental conditions for optimal heating. We find that systems with low-thermal-fluctuation influence are better candidates for the application due to their high SPA values. © 2021 American Physical Society