Dielectric spectrum of a ferrofluid layer exposed to a gradient magnetic field.

A low-frequency dielectric response of a ferrofluid based on transformer oil and MnZn ferrite nanoparticles is investigated in a gradient magnetic field. Four ferrofluid samples of various nanoparticle concentrations were introduced into planar micro-capacitors located over a magnetized tip. The dielectric spectra were measured in the frequency range from 0.1 Hz to 200 kHz and in the local magnetic field up to 100 mT. The spectra exhibit a dielectric relaxation ascribed to nanoparticle interfacial polarization. The low-frequency spectrum of each ferrofluid decreases upon application of the magnetic field up to 20 mT. The decrease in dielectric permittivity is caused by a magnetic force acting on larger nanoparticles in the gradient magnetic field. It is assumed that the interfaces of the concentrated nanoparticles in the gradient field do not contribute to the effective dielectric response. This reduces the effective relaxation time and shifts the relaxation toward higher frequencies. The dielectric spectra are well described by a relaxation fit function consisting of one Havriliak-Negami and a conductivity term. The fitting confirms that the only effect of the gradient magnetic field on the dielectric spectra is the shift of the dielectric relaxation and the decrease of the amplitude in the imaginary permittivity. This behavior is evident from a master plot, where all dielectric relaxations are superimposed on a single line. The knowledge of the presented behavior of the ferrofluid may be valuable when applying a ferrofluid to sharply magnetized parts of various electrical equipment (wires, tips, screws, nails, edges) as a liquid dielectric medium.

Surface acoustic wave investigation of magnetic nanoparticle size and concentration effect on liquid crystal behavior.

The effect of spherical magnetic nanoparticles with different size (5, 10, 15, and 20 nm) and volume concentration (10-3, 5 × 10-4, and 10-4) on liquid crystal 4-cyano-4'-hexylbiphenyl (6CB) behavior was investigated using surface acoustic wave (SAW). The attenuation response of SAW propagating along with the substrate/liquid crystal interface was used to study the structural changes induced by an applied magnetic field. The obtained results showed the shift of the threshold magnetic field with an increase in the volume concentration of nanoparticles toward lower fields and also the decrease in the isotropic-nematic phase transition temperature depending on the nanoparticle size and the nanoparticle volume fraction. Results confirmed again that the bulk viscosity coefficients should dominate the SAW attenuation and that the SAW investigation in the presented configuration is applicable to monitoring of the role of magnetic dopants in structural changes under external fields. Some theoretical background of the presented SAW investigation is introduced as well. Obtained results are discussed within the context of previous ones.

Destruction of Lysozyme Amyloid Fibrils Induced by Magnetoferritin and Reconstructed Ferritin.

Neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), or systemic amyloidosis, are characterized by the specific protein transformation from the native state to stable insoluble deposits, e.g., amyloid plaques. The design of potential therapeutic agents and drugs focuses on the destabilization of the bonds in their beta-rich structures. Surprisingly, ferritin derivatives have recently been proposed to destabilize fibril structures. Using atomic force microscopy (AFM) and fluorescence spectrophotometry, we confirmed the destructive effect of reconstructed ferritin (RF) and magnetoferritin (MF) on lysosome amyloid fibrils (LAF). The presence of iron was shown to be the main factor responsible for the destruction of LAF. Moreover, we found that the interaction of RF and MF with LAF caused a significant increase in the release of potentially harmful ferrous ions. Zeta potential and UV spectroscopic measurements of LAF and ferritin derivative mixtures revealed a considerable difference in RF compared to MF. Our results contribute to a better understanding of the mechanism of fibril destabilization by ferritin-like proteins. From this point of view, ferritin derivatives seem to have a dual effect: therapeutic (fibril destruction) and adverse (oxidative stress initiated by increased Fe2+ release). Thus, ferritins may play a significant role in various future biomedical applications.

Tuning of Magnetic Hyperthermia Response in the Systems Containing Magnetosomes.

A number of materials are studied in the field of magnetic hyperthermia. In general, the most promising ones appear to be iron oxide particle nanosystems. This is also indicated in some clinical trial studies where iron-based oxides were used. On the other hand, the type of material itself provides a number of variations on how to tune hyperthermia indicators. In this paper, magnetite nanoparticles in various forms were analyzed. The nanoparticles differed in the core size as well as in the form of their arrangement. The arrangement was determined by the nature of the surfactant. The individual particles were covered chemically by dextran; in the case of chain-like particles, they were encapsulated naturally in a lipid bilayer. It was shown that in the case of chain-like nanoparticles, except for relaxation, a contribution from magnetic hysteresis to the heating process also appears. The influence of the chosen methodology of magnetic field generation was also analyzed. In addition, the influence of the chosen methodology of magnetic field generation was analyzed. The application of a rotating magnetic field was shown to be more efficient in generating heat than the application of an alternating magnetic field. However, the degree of efficiency depended on the arrangement of the magnetite nanoparticles. The difference in the efficiency of the rotating magnetic field versus the alternating magnetic field was much more pronounced for individual nanoparticles (in the form of a magnetic fluid) than for systems containing chain nanoparticles (magnetosomes and a mix of magnetic fluid with magnetosomes in a ratio 1:1).

Longitudinal and Transverse Relaxivity Analysis of Native Ferritin and Magnetoferritin at 7 T MRI.

Magnetite mineralization in human tissue is associated with various pathological processes, especially neurodegenerative disorders. Ferritin's mineral core is believed to be a precursor of magnetite mineralization. Magnetoferritin (MF) was prepared with different iron loading factors (LFs) as a model system for pathological ferritin to analyze its MRI relaxivity properties compared to those of native ferritin (NF). The results revealed that MF differs statistically significantly from NF, with the same LF, for all studied relaxation parameters at 7 T: r1, r2, r2*, r2/r1, r2*/r1. Distinguishability of MF from NF may be useful in non-invasive MRI diagnosis of pathological processes associated with iron accumulation and magnetite mineralization (e.g., neurodegenerative disorders, cancer, and diseases of the heart, lung and liver). In addition, it was found that MF samples possess very strong correlation and MF's relaxivity is linearly dependent on the LF, and the transverse and longitudinal ratios r2/r1 and r2*/r1 possess complementary information. This is useful in eliminating false-positive hypointensive artefacts and diagnosis of the different stages of pathology. These findings could contribute to the exploitation of MRI techniques in the non-invasive diagnosis of iron-related pathological processes in human tissue.

The Impact of Redox, Hydrolysis and Dehydration Chemistry on the Structural and Magnetic Properties of Magnetoferritin Prepared in Variable Thermal Conditions.

Ferritin, a spherically shaped protein complex, is responsible for iron storage in bacteria, plants, animals, and humans. Various ferritin iron core compositions in organisms are associated with specific living requirements, health state, and different biochemical roles of ferritin isomers. Magnetoferritin, a synthetic ferritin derivative, serves as an artificial model system of unusual iron phase structures found in humans. We present the results of a complex structural study of magnetoferritins prepared by controlled in vitro synthesis. Using various complementary methods, it was observed that manipulation of the synthesis technology can improve the physicochemical parameters of the system, which is useful in applications. Thus, a higher synthesis temperature leads to an increase in magnetization due to the formation of the magnetite phase. An increase in the iron loading factor has a more pronounced impact on the protein shell structure in comparison with the pH of the aqueous medium. On the other hand, a higher loading factor at physiological temperature enhances the formation of an amorphous phase instead of magnetite crystallization. It was confirmed that the iron-overloading effect alone (observed during pathological events) cannot contribute to the formation of magnetite.

Dependence of the Nanoscale Composite Morphology of Fe3O4 Nanoparticle-Infused Lysozyme Amyloid Fibrils on Timing of Infusion: A Combined SAXS and AFM Study.

Understanding the formation process and the spatial distribution of nanoparticle (NP) clusters on amyloid fibrils is an essential step for the development of NP-based methods to inhibit aggregation of amyloidal proteins or reverse the assembling trend of the proto-fibrillary complexes that prompts pathogenesis of neuro degeneration. For this, a detailed structural determination of the diverse hybrid assemblies that are forming is needed, which can be achieved by advanced X-ray scattering techniques. Using a combined solution small angle X-ray scattering (SAXS) and atomic force microscopy (AFM) approach, this study investigates the intrinsic trends of the interaction between lysozyme amyloid fibrils (LAFs) and Fe3O4 NPs before and after fibrillization at nanometer resolution. AFM images reveal that the number of NP clusters interacting with the lysozyme fibers does not increase significantly with NP volume concentration, suggesting a saturation in NP aggregation on the fibrillary surface. The data indicate that the number of non-adsorbed Fe3O4 NPs is highly dependent on the timing of NP infusion within the synthesis process. SAXS data yield access to the spatial distribution, aggregation manner and density of NP clusters on the fibrillary surfaces. Employing modern data analysis approaches, the shape and internal structural morphology of the so formed nanocomposites are revealed. The combined experimental approach suggests that while Fe3O4 NPs infusion does not prevent the fibril-formation, the variation of NP concentration and size at different stages of the fibrillization process can impose a pronounced impact on the superficial and internal structural morphologies of these nanocomposites. These findings may be applicable in devising advanced therapeutic treatments for neurodegenerative diseases and designing novel bio-inorganic magnetic devices. Our results further demonstrate that modern X-ray methods give access to the structure of-and insight into the formation process of-biological-inorganic hybrid structures in solution.

Effect of the concentration of protein and nanoparticles on the structure of biohybrid nanocomposites.

We present colloidal nanocomposites formed by incorporating magnetite Fe3 O4 nanoparticles (MNPs) with lysozyme amyloid fibrils (LAFs). Preparation of two types of solutions, with and without addition of salt, was carried out to elucidate the structure of MNPs-incorporated fibrillary nanocomposites and to study the effect of the presence of salt on the stability of the nanocomposites. The structural morphology of the LAFs and their interaction with MNPs were analyzed by atomic force microscopy and small-angle x-ray scattering measurements. The results indicate that conformational properties of the fibrils are dependent on the concentration of protein, and the precise ratio of the concentration of the protein and MNPs is crucially important for the stability of the fibrillary nanocomposites. Our results confirm that despite the change in fibrillary morphology induced by the varying concentration of the protein, the adsorption of MNPs on the surface of LAF is morphologically independent. Moreover, most importantly, the samples containing salt have excellent stability for up to 1 year of shelf-life.

Quantification of Iron Release from Native Ferritin and Magnetoferritin Induced by Vitamins B2 and C.

Various pathological processes in humans are associated with biogenic iron accumulation and the mineralization of iron oxide nanoparticles, especially magnetite. Ferritin has been proposed as a precursor to pathological magnetite mineralization. This study quantifies spectroscopically the release of ferrous ions from native ferritin and magnetoferritin as a model system for pathological ferritin in the presence of potent natural reducing agents (vitamins C and B2) over time. Ferrous cations are required for the transformation of ferrihydrite (physiological) into a magnetite (pathological) mineral core and are considered toxic at elevated levels. The study shows a significant difference in the reduction and iron release from native ferritin compared to magnetoferritin for both vitamins. The amount of reduced iron formed from a magnetoferritin mineral core is two to five times higher than from native ferritin. Surprisingly, increasing the concentration of the reducing agent affects only iron release from native ferritin. Magnetoferritin cores with different loading factors seem to be insensitive to different concentrations of vitamins. An alternative hypothesis of human tissue magnetite mineralization and the process of iron-induced pathology is proposed. The results could contribute to evidence of the molecular mechanisms of various iron-related pathologies, including neurodegeneration.

Tuning the phase transition temperature of ferronematics with a magnetic field.

The influence of magnetic field on the isotropic-to-nematic phase transition temperature is investigated in neat bent-core and calamitic liquid crystals, in their mixture, and in samples doped with spherical magnetic nanoparticles for two different orientations of the magnetic field. A magnetic-field-induced negative or positive shift of the transition temperature was detected depending on the magnetic field orientation with respect to the initial orientation of the nematic phase, and on the type of liquid crystal matrix.

Fe(II) formation after interaction of the amyloid ß-peptide with iron-storage protein ferritin.

The interaction of amyloid ß-peptide (Aß) with the iron-storage protein ferritin was studied in vitro. We have shown that Aß during fibril formation process is able to reduce Fe(III) from the ferritin core (ferrihydrite) to Fe(II). The Aß-mediated Fe(III) reduction yielded a two-times-higher concentration of free Fe(II) than the spontaneous formation of Fe(II) by the ferritin itself. We suggest that Aß can also act as a ferritin-specific metallochaperone-like molecule capturing Fe(III) from the ferritin ferrihydrite core. Our observation may partially explain the formation of Fe(II)-containing minerals in human brains suffering by neurodegenerative diseases.

Magnetic field sensing using whispering-gallery modes in a cylindrical microresonator infiltrated with ferronematic liquid crystal.

An all-fiber magnetic field sensor based on whispering-gallery modes (WGM) in a fiber micro-resonator infiltrated with ferronematic liquid crystal is proposed and experimentally demonstrated. The cylindrical microresonator is formed by a 1 cm-long section of a photonic crystal fiber infiltrated with ferronematic materials. Both ferronematics suspensions are prepared based on the nematic liquid crystal 1-(trans-4-Hexylcyclohexyl)-4-isothiocyanatobenzene (6CHBT) doped with rod-like magnetic particles in the first case and with spherical magnetic particles in the second case. WGMs are excited in the fiber microresonator by evanescent light coupling using a tapered fiber with a micron-size diameter. The Q-factor of the microresonator determined from the experimentaly measured transmission spectrum of the tapered fiber was 1.975 × 103. Under the influence of an applied magnetic field the WGM resonances experience spectral shift towards shorter wavelengths. The experimentally demonstrated sensitivity of the proposed sensor was -39.6 pm/mT and -37.3 pm/mT for samples infiltrated with rod like and spherical like ferromagnetic suspensions respectively for a magnetic field range (0-47) mT. Reducing the diameter of the cylindrical micro-resonator by tapering leads to enhancement of the magnetic field sensitivity up to -61.86 pm/mT and -49.88 pm/mT for samples infiltrated with rod like and spherical like ferromagnetic suspensions respectively for the magnetic field range (0-44.7) mT.

Structuralization of magnetic nanoparticles in 5CB liquid crystals.

This work is devoted to the study of highly stable composite systems of the liquid crystal 4-n-pentyl-4'-cyanobiphenyl (5CB) doped with CoFe2O4 magnetic nanoparticles. Ferronematic samples were prepared with two different weight concentrations: sample A 0.085 wt% and sample B 0.062 wt%. The interaction of CoFe2O4 nanoparticles with the liquid crystal was investigated by small-angle X-ray-scattering and magnetization measurements. The obtained results reveal aggregates formed by magnetic nanoparticles that are oriented in the nematic phase. Moreover, the prepared samples show unexpected behaviour of a sudden change in magnetization, which is unusual for such ferronematics.

Electrode polarization and unusual magnetodielectric effect in a transformer oil-based magnetic nanofluid thin layer.

In the present paper, we provide low-frequency dielectric spectra for a thin layer of a nanofluid based on transformer oil and iron oxide nanoparticles stabilized by oleic acid. The complex dielectric permittivity measured in the frequency range from 1 mHz to 200 kHz shows an obvious electrode polarization effect and a Debye-like dielectric relaxation process. Both effects stem from the presence of space charge in the oil due to impurity ions, and in the nanofluid represented predominantly by a residual surfactant and uncompensated particle surface charge. It is shown that the spectra, which were measured in the temperature range from 298 K to 358 K, can be well represented by a fitting function consisted of one Havriliak-Negami term and the Jonscher's power law. In the investigated magnetic nanofluid layer, we found that the onset of the electrode polarization is suppressed to lower frequencies by the application of an external magnetic field (300 mT). This phenomenon is explained by a slowed-down migration of the space charge due to the Lorentz force and by a hindering effect of the formed magnetic nanoparticle aggregates. Surprisingly, a moderate decrease in the whole permittivity spectrum was observed for both parallel and perpendicular orientations of the electric and magnetic fields. This is in contradiction with the usual magnetodielectric anisotropy effect. Based on our qualitative analysis, we discuss potential reasons accountable for the observed effect.

Biasing a ferronematic - a new way to detect weak magnetic field.

The magnetic properties of a ferronematic, i.e., a nematic liquid crystal doped with magnetic nanoparticles in low volume concentration are studied, with the focus on the ac magnetic susceptibility. A weak dc bias magnetic field (a few Oe) applied to the ferronematic in its isotropic phase increases the ac magnetic susceptibility considerably. Passage of the isotropic-to-nematic phase transition resets this enhancement irreversibly (unless the dc bias field is applied again in the isotropic phase).

Attenuation of the insulin amyloid aggregation in presence of Fe3O4-based magnetic fluids.

Presence of protein amyloid deposits is associated with pathogenesis of amyloid-related diseases. Insulin amyloid aggregates have been reported in a patient with diabetes undergoing treatment by injection of insulin. We have investigated the interference of insulin amyloid aggregation with two Fe3O4-based magnetic fluids. The magnetic fluids are able to inhibit insulin amyloid fibrillization and promote disassembly of amyloid fibrils. The cytotoxic effect of amyloid fibrils is attenuated in presence of magnetic fluids probably due to reduction of the fibrils. We suggest that present findings propose the potential use of Fe3O4-based magnetic fluids as the therapeutic agents targeting insulin-associating amyloidosis.

Study on the Memory Effect in Aerosil-Filled Nematic Liquid Crystal Doped with Magnetic Nanoparticles.

A study on 5CB liquid crystal composites with SiO2 nanoparticles and an additional commixture with Fe3O4 nanoparticles using light transmission and SAW measurements is presented. The prepared liquid crystal composites exhibited an interesting memory effect characterized by the hysteresis of both light transmission and SAW attenuation responses investigated in the nematic phase. While in the case of SiO2 nanoparticles as dopants, the liquid crystal composite showed an improvement in the memory effect, the addition of Fe3O4 magnetic nanoparticles resulted in the memory effect decreasing. Additional studies showed a significant shift in both the threshold voltage and nematic-isotropic transition temperature. Measurements in the magnetic field confirmed the increasing memory effect according to that of pure 5CB. The properties of these composites could lead to a potential application for the fabrication of memory devices suitable for information storage.

Depolymerization of insulin amyloid fibrils by albumin-modified magnetic fluid.

Pathogenesis of amyloid-related diseases is associated with the presence of protein amyloid deposits. Insulin amyloids have been reported in a patient with diabetes undergoing treatment by injection of insulin and causes problems in the production and storage of this drug and in pplication of insulin pumps. We have studied the interference of insulin amyloid fibrils with a series of 18 albumin magnetic fluids (MFBSAs) consisting of magnetite nanoparticles modified by different amounts of bovine serum albumin (w/w BSA/Fe3O4 from 0.005 up to 15). We have found that MFBSAs are able to destroy amyloid fibrils in vitro. The extent of fibril depolymerization was affected by nanoparticle physical-chemical properties (hydrodynamic diameter, zeta potential and isoelectric point) determined by the BSA amount present in MFBSAs. The most effective were MFBSAs with lower BSA/Fe3O4 ratios (from 0.005 to 0.1) characteristic of about 90% depolymerizing activity. For the most active magnetic fluids (ratios 0.01 and 0.02) the DC50 values were determined in the range of low concentrations, indicating their ability to interfere with insulin fibrils at stoichiometric concentrations. We assume that the present findings represent a starting point for the application of the active MFBSAs as therapeutic agents targeting insulin amyloidosis.

Role of Magnetic Nanoparticles Size and Concentration on Structural Changes and Corresponding Magneto-Optical Behavior of Nematic Liquid Crystals.

The effect of magnetic nanoparticles size and concentration on nematic liquid crystal (NLC) behavior in a magnetic field was investigated. The magneto-optical investigation using measurements of the light transmission through the liquid crystal was used to study the structural changes induced by an applied weak magnetic field. Magnetic nanoparticles Fe3O4 of spherical shape with different size and volume concentration were added to NLC 4-cyano-40 -hexylbiphenyl (6CB) during its isotropic phase. In contrast to undoped liquid crystals, the distinctive different light transmission responses induced by a magnetic field in studied NLC samples were observed suggesting both structural changes and the orientational coupling between magnetic moments of nanoparticles and the director of the NLC. Experimental measurements were conducted, including investigation under linearly increasing and/or jumped magnetic field, respectively, as well as the investigation of time influence on structural changes to study their stability and switching time. The analysis of observed light transmission characteristics confirmed the role of concentration and size of magnetic nanoparticles on the resultant behavior of investigated NLC compounds. The obtained results showed the lowering of the threshold magnetic field with an increase in the volume concentration of nanoparticles and on the important role of nanoparticles size on stability and switching properties. Obtained results are discussed within the context of previous ones.

Endovascular administration of magnetized nanocarriers targeting brain delivery after stroke.

The increasing use of mechanical thrombectomy in stroke management has opened the window to local intraarterial brain delivery of therapeutic agents. In this context, the use of nanomedicine could further improve the delivery of new treatments for specific brain targeting, tracking and guidance. In this study we take advantage of this new endovascular approach to deliver biocompatible poly(D-L-lactic-co-glycolic acid) (PLGA) nanocapsules functionalized with superparamagnetic iron oxide nanoparticles and Cy7.5 for magnetic targeting, magnetic resonance and fluorescent molecular imaging. A complete biodistribution study in naïve (n = 59) and ischemic (n = 51) mice receiving intravenous or intraarterial nanocapsules, with two different magnet devices and imaged from 30 min to 48 h, showed an extraordinary advantage of the intraarterial route for brain delivery with a specific improvement in cortical targeting when using a magnetic device in both control and ischemic conditions. Safety was evaluated in ischemic mice (n = 69) showing no signs of systemic toxicity nor increasing mortality, infarct lesions or hemorrhages. In conclusion, the challenging brain delivery of therapeutic nanomaterials could be efficiently and safely overcome with a controlled endovascular administration and magnetic targeting, which could be considered in the context of endovascular interventions for the delivery of multiple treatments for stroke.