Cell bystander effect induced by radiofrequency electromagnetic fields and magnetic nanoparticles

Induced effects by direct exposure to ionizing radiation (IR) are a central issue in many fields like radiation protection, clinic diagnosis and oncological therapies. Direct irradiation at certain doses induce cell death, but similar effects can also occur in cells no directly exposed to IR, a mechanism known as bystander effect. Non-IR (radiofrequency waves) can induce the death of cells loaded with MNPs in a focused oncological therapy known as magnetic hyperthermia. Indirect mechanisms are also able to induce the death of unloaded MNPs cells. Using in vitro cell models, we found that colocalization of the MNPs at the lysosomes and the non-increase of the temperature induces bystander effect under non-IR. Our results provide a landscape in which bystander effects are a more general mechanism, up to now only observed and clinically used in the field of radiotherapy.Comment: 16 pages, 4 figures, submitted to International Journal of Radiation Biolog

Sarcopenic Obesity and Cardiometabolic Health and Mortality in Older Adults: a Growing Health Concern in an Ageing Population

PURPOSE OF REVIEW: Sarcopenic obesity (SO) is a growing public health problem in older adults. Whether SO confers higher risk of cardiometabolic disease and mortality than obesity or sarcopenia alone is still a matter of debate. We focus on recent findings on SO and cardiometabolic health and mortality in older adults. RECENT FINDINGS: SO is associated with increased mortality compared to non-sarcopenic obesity, but similar mortality risk compared to sarcopenia without obesity. SO is associated with a higher risk of cardiovascular disease (CVD), diabetes, and physical disability than obesity or sarcopenia alone. SO, in the presence of diabetes, is associated with the highest risk of CVD and chronic kidney disease. A definition and diagnostic criteria for SO has recently been proposed (ESPEN and EASO). SO is associated with more adverse outcomes overall than sarcopenia or obesity alone. Future research is required to assess the impact of the new SO definition on health outcomes

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

Magnetic hyperthermia in single-domain monodisperse FeCo nanoparticles: Evidences for Stoner-Wohlfarth behaviour and large losses

We report on hyperthermia measurements on a colloidal solution of 15 nm monodisperse FeCo nanoparticles (NPs). Losses as a function of the magnetic field display a sharp increase followed by a plateau, which is what is expected for losses of ferromagnetic single-domain NPs. The frequency dependence of the coercive field is deduced from hyperthermia measurement and is in quantitative agreement with a simple model of non-interacting NPs. The measured losses (1.5 mJ/g) compare to the highest of the literature, though the saturation magnetization of the NPs is well below the bulk one.Comment: 14 pages, 3 figure

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