397 research outputs found
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
Protein adsorption onto Fe3O4 nanoparticles with opposite surface charge and its impact on cell uptake
Nanoparticles (NPs) engineered for biomedical applications are meant to be in
contact with protein-rich physiological fluids. These proteins are usually
adsorbed onto the NP surface, forming a swaddling layer called protein corona
that influences cell internalization. We present a study on protein adsorption
onto different magnetic NPs (MNPs) when immersed in cell culture medium, and
how these changes affect the cellular uptake. Two colloids with magnetite cores
of 25 nm, same hydrodynamic size and opposite surface charge were in situ
coated with (a) positive polyethyleneimine (PEI-MNPs) and (b) negative
poly(acrylic acid) (PAA-MNPs). After few minutes of incubation in cell culture
medium the wrapping of the MNPs by protein adsorption resulted in a 5-fold size
increase. After 24 h of incubation large MNP-protein aggregates with
hydrodynamic sizes 1500 to 3000 nm (PAA-MNPs and PEI-MNPs respectively) were
observed. Each cluster contained an estimated number of magnetic cores between
450 and 1000, indicating the formation of large aggregates with a "plum
pudding" structure of MNPs embedded into a protein network of negative surface
charge irrespective of the MNP_core charge. We demonstrated that PEI-MNPs are
incorporated in much larger amounts than the PAA-MNPs units. Quantitative
analysis showed that SH-SY5Y cells can incorporate 100 per cent of the added
PEI-MNPs up to about 100 pg per cell, whereas for PAA-MNPs the uptake was less
than 50 percent. The final cellular distribution showed also notable
differences regarding partial attachment to the cell membrane. These results
highlight the need to characterize the final properties of MNPs after protein
adsorption in biological media, and demonstrate the impact of these properties
on the internalization mechanisms in neural cells.Comment: 32 pages, 10 figure
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
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
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