T. E. Torres

Magnetic nanoparticles for power absorption: Optimizing size, shape and magnetic properties

We present a study on the magnetic properties of naked and silica-coated Fe{sub 3}O{sub 4} nanoparticles with sizes between 5 and 110 nm. Their efficiency as heating agents was assessed through specific power absorption (SPA) measurements as a function of particle size and shape. The results show a strong dependence of the SPA with the particle size, with a maximum around 30 nm, as expected for a Neel relaxation mechanism in single-domain particles. The SiO{sub 2} shell thickness was found to play an important role in the SPA mechanism by hindering the heat outflow, thus decreasing the heating efficiency. It is concluded that a compromise between good heating efficiency and surface functionality for biomedical purposes can be attained by making the SiO{sub 2} functional coating as thin as possible. - Graphical Abstract: The magnetic properties of Fe{sub 3}O{sub 4} nanoparticles from 5 to 110 nm are presented, and their efficiency as heating agents discussed as a function of particle size, shape and surface functionalization.

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 number of MNPs incorporated into the cytoplasm was measured by magnetometry, which confirmed that 1-5 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 (NH(2)(+)) or negative (COOH(-)) surface functional groups. In spite of the massive cell death induced by application of AMF to MNP-loaded DCs, the number 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.

Poly-l-lysine-coated magnetic nanoparticles as intracellular actuators for neural guidance

Purpose It has been proposed in the literature that Fe3O4 magnetic nanoparticles (MNPs) could be exploited to enhance or accelerate nerve regeneration and to provide guidance for regenerating axons. MNPs could create mechanical tension that stimulates the growth and elongation of axons. Particles suitable for this purpose should possess (1) high saturation magnetization, (2) a negligible cytotoxic profile, and (3) a high capacity to magnetize mammalian cells. Unfortunately, the materials currently available on the market do not satisfy these criteria; therefore, this work attempts to overcome these deficiencies. Methods Magnetite particles were synthesized by an oxidative hydrolysis method and characterized based on their external morphology and size distribution (high-resolution transmission electron microscopy [HR-TEM]) as well as their colloidal (Z potential) and magnetic properties (Superconducting QUantum Interference Devices [SQUID]). Cell viability was assessed via Trypan blue dye exclusion assay, cell doubling time, and MTT cell proliferation assay and reactive oxygen species production. Particle uptake was monitored via Prussian blue staining, intracellular iron content quantification via a ferrozine-based assay, and direct visualization by dual-beam (focused ion beam/scanning electron microscopy [FIB/SEM]) analysis. Experiments were performed on human neuroblastoma SH-SY5Y cell line and primary Schwann cell cultures of the peripheral nervous system. Results This paper reports on the synthesis and characterization of polymer-coated magnetic Fe3O4 nanoparticles with an average diameter of 73 ± 6 nm that are designed as magnetic actuators for neural guidance. The cells were able to incorporate quantities of iron up to 2 pg/cell. The intracellular distribution of MNPs obtained by optical and electronic microscopy showed large structures of MNPs crossing the cell membrane into the cytoplasm, thus rendering them suitable for magnetic manipulation by external magnetic fields. Specifically, migration experiments under external magnetic fields confirmed that these MNPs can effectively actuate the cells, thus inducing measurable migration towards predefined directions more effectively than commercial nanoparticles (fluidMAG-ARA supplied by Chemicell). There were no observable toxic effects from MNPs on cell viability for working concentrations of 10 μg/mL (EC25 of 20.8 μg/mL, compared to 12 μg/mL in fluidMAG-ARA). Cell proliferation assays performed with primary cell cultures of the peripheral nervous system confirmed moderate cytotoxicity (EC25 of 10.35 μg/mL). Conclusion These results indicate that loading neural cells with the proposed MNPs is likely to be an effective strategy for promoting non-invasive neural regeneration through cell magnetic actuation.

Magnetic Hydrogels Derived from Polysaccharides with Improved Specific Power Absorption: Potential Devices for Remotely Triggered Drug Delivery

We report on novel ferrogels derived from polysaccharides (sodium alginate and chitosan) with embedded iron oxide nanoparticles synthesized in situ and their combination with thermally responsive poly(N-isopropylacrylamide) for externally driven drug release using AC magnetic fields. Samples were characterized by Raman spectroscopy, transmission electron microscopy, and magnetic measurements. The obtained nanoparticles were found to be of ∼10 nm average size, showing magnetic properties very close to those of the bulk material. The thermal response was measured by power absorption experiments, finding specific power absorption values between 100 and 300 W/g, which was enough for attaining the lower critical solution temperature of the polymeric matrix within few minutes. This fast response makes these materials good candidates for externally controlled drug release.

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 ≤ T B ≤ 320 K, reflecting the large magnetocrystalline anisotropy of these nanoparticles. Accordingly, high coercive fields HC ≈ 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 ≈ 12 nm.

Neuronal cells loaded with PEI-coated Fe3O4 nanoparticles for magnetically guided nerve regeneration

We report a one-step synthesis protocol for obtaining polymer-coated magnetic nanoparticles (MNPs) engineered for uploading neural cells. Polyethyleneimine-coated Fe3O4 nanoparticles (PEI-MNPs) with sizes of 25 ± 5 nm were prepared by oxidation of Fe(OH)2 by nitrate in basic aqueous media and adding PEI in situ during synthesis. The obtained PEI-MNP cores displayed a neat octahedral morphology and high crystallinity. The resulting nanoparticles were coated with a thin polymer layer of about 0.7-0.9 nm, and displayed a saturation magnetization value MS = 58 A m2 kg-1 at 250 K (64 A m2 kg-1 for T = 10 K). Cell uptake experiments on a neuroblastoma-derived SH-SY5Y cell line were undertaken over a wide time and MNP concentration range. The results showed a small decrease in cell viability for 24 h incubation (down to 70% viability for 100 μg ml-1), increasing the toxic effects with incubation time (30% cell survival at 100 μg ml-1 for 7 days of incubation). On the other hand, primary neuronal cells displayed higher sensitivity to PEI-MNPs, with a cell viability reduction of 44% of the control cells after 3 days of incubation with 50 μg ml-1. The amount of PEI-MNPs uploaded by SH-SY5Y cells was found to have a linear dependence on concentration. The intracellular distribution of the PEI-MNPs analyzed at the single-cell level by the dual-beam (FIB/SEM) technique revealed the coexistence of both fully incorporated PEI-MNPs and partially internalized PEI-MNP-clusters crossing the cell membrane. The resulting MNP-cluster distributions open the possibility of using these PEI-MNPs for magnetically driven axonal re-growth in neural cells.

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

Background Magnetic hyperthermia is currently a clinical therapy approved in the European Union for treatment of tumor cells, and uses magnetic nanoparticles (MNPs) under time-varying magnetic fields (TVMFs). The same basic principle seems promising against trypanosomatids causing Chagas disease and sleeping sickness, given that the therapeutic drugs available have severe side effects and that there are 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 Fe3O4 MNPs in order to provoke cell death remotely using TVMFs. Methods Iron oxide MNPs with average diameters of approximately 30 nm were synthesized by precipitation of FeSO4 in basic medium. The MNPs were added to C. fasciculata choanomastigotes in the exponential phase and incubated overnight, removing excess MNPs using a DEAE-cellulose resin column. The amount of MNPs uploaded per cell was determined by magnetic measurement. The cells bearing MNPs were submitted to TVMFs using a homemade AC field applicator (f = 249 kHz, H = 13 kA/m), and the temperature variation during the experiments was measured. Scanning electron microscopy was used to assess morphological changes after the TVMF experiments. Cell viability was analyzed using an MTT colorimetric assay and flow cytometry. Results MNPs were incorporated into the cells, with no noticeable cytotoxicity. When a TVMF was applied to cells bearing MNPs, massive cell death was induced via a nonapoptotic mechanism. No effects were observed by applying TVMF to control cells not loaded with MNPs. No macroscopic rise in temperature was observed in the extracellular medium during the experiments. Conclusion As a proof of principle, these data indicate that intracellular hyperthermia is a suitable technology to induce death of protozoan parasites bearing MNPs. These findings expand the possibilities for new therapeutic strategies combating parasitic infection.

The orientation of the neuronal growth process can be directed via magnetic nanoparticles under an applied magnetic field

There is a growing body of evidence indicating the importance of physical stimuli for neuronal growth and development. Specifically, results from published experimental studies indicate that forces, when carefully controlled, can modulate neuronal regeneration. Here, we validate a non-invasive approach for physical guidance of nerve regeneration based on the synergic use of magnetic nanoparticles (MNPs) and magnetic fields (Ms). The concept is that the application of a tensile force to a neuronal cell can stimulate neurite initiation or axon elongation in the desired direction, the MNPs being used to generate this tensile force under the effect of a static external magnetic field providing the required directional orientation. In a neuron-like cell line, we have confirmed that MNPs direct the neurite outgrowth preferentially along the direction imposed by an external magnetic field, by inducing a net angle displacement (about 30°) of neurite direction. From the clinical editor: This study validates that non-invasive approaches for physical guidance of nerve regeneration based on the synergic use of magnetic nanoparticles and magnetic fields are possible. The hypothesis was confirmed by observing preferential neurite outgrowth in a cell culture system along the direction imposed by an external magnetic field.

Validity of the Néel-Arrhenius model for highly anisotropic CoxFe3−xO4 nanoparticles

We report a systematic study on the structural and magnetic properties of CoxFe3−xO4 magnetic nanoparticles with sizes between 5 and 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 < TB < 345 K for 5 < d < 13 nm) and large coercive fields (HC ≈ 1600 kA/m for T = 5 K). The smallest particles (⟨d⟩=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 Neel–Arrhenius relaxation framework by including the thermal dependence of the magnetocrystalline anisotropy constant K1(T), without the need of ad-hoc corrections. This approach, using the empirical Brukhatov-Kirensky relation, provided K1(0) values very similar to the bulk material from either static or dynamic magnetic measurements, as well as realistic values for the response times (τ0 ≈ 10−10s). Deviations from the bulk anisotropy values found for the smallest particles could be qualitatively explained based on Zeners relation between K1(T) and M(T).

Development and evaluation of 90Y-labeled albumin microspheres loaded with magnetite nanoparticles for possible applications in cancer therapy

Radiolabeled albumin microspheres with encapsulated citric acid-coated magnetite nanoparticles were developed as a targeting approach to localize both radioactivity and magnetic energy at the tumor site. We present in vitro and in vivo studies of yttrium-90 (90Y)-labeled human serum albumin magnetic microspheres (HSAMMS) as a multifunctional agent for possible applications in a bimodal radionuclide-hyperthermia cancer therapy. The HSAMMS were produced using a modified emulsification-heat stabilization technique and contained 11 nm magnetite nanoparticles coated with citric acid, distributed as inhomogeneous clusters within the albumin microspheres. The size, size distribution and the morphology of magnetite nanoparticles and HSAMMS were determined by FESEM, HRTEM and SEM/FIB dual beam. The average particle size of the complete HSAMMS was 20 μm, and they exhibited superparamagnetic behavior at room temperature. The in vitro experiments (in saline and human serum) revealed the high stability of the labeled HSAMMS in saline and human serum after 72 h. Following the intravenous administration of the 90Y-HSAMMS in rats, 88.81% of the activity localizes in the lungs after 1 h, with 82.67% remaining after 72 h. These data on 90Y-HSAMMS provide good evidence for their potential use in bimodal radionuclide-hyperthermia cancer therapy.