Martina Kubovcikova

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.

Acoustic wave in a suspension of magnetic nanoparticle with sodium oleate coating

The ultrasonic propagation in the water-based magnetic fluid with doubled layered surfactant shell was studied. The measurements were carried out both in the presence as well as in the absence of the external magnetic field. The thickness of the surfactant shell was evaluated by comparing the mean size of magnetic grain extracted from magnetization curve with the mean hydrodynamic diameter obtained from differential centrifugal sedimentation method. The thickness of surfactant shell was used to estimate volume fraction of the particle aggregates consisted of magnetite grain and surfactant layer. From the ultrasonic velocity measurements in the absence of the applied magnetic field, the adiabatic compressibility of the particle aggregates was determined. In the external magnetic field, the magnetic fluid studied in this article becomes acoustically anisotropic, i.e., velocity and attenuation of the ultrasonic wave depend on the angle between the wave vector and the direction of the magnetic field. The results of the ultrasonic measurements in the external magnetic field were compared with the hydrodynamic theory of Ovchinnikov and Sokolov (velocity) and with the internal chain dynamics model of Shliomis, Mond and Morozov (attenuation).

Magnetic nanoparticles for enhancing the effectiveness of ultrasonic hyperthermia

Ultrasonic hyperthermia is a method of cancer treatment in which tumors are exposed to an elevated cytotoxic temperature using ultrasound (US). In conventional ultrasonic hyperthermia, the ultrasound-induced heating in the tumor is achieved through the absorption of wave energy. However, to obtain appropriate temperature in reasonable time, high US intensities, which can have a negative impact on healthy tissues, are required. The effectiveness of US for medical purposes can be significantly improved by using the so-called sonosensitizers, which can enhance the thermal effect of US on the tissue by increasing US absorption. One possible candidate for such sonosensitizers is magnetic nanoparticles with mean sizes of 10–300 nm, which can be efficiently heated because of additional attenuation and scattering of US. Additionally, magnetic nanoparticles are able to produce heat in the alternating magnetic field (magnetic hyperthermia). The synergetic application of ultrasonic and magnetic hyperthermia can lead...

d,l-lysine functionalized Fe3O4 nanoparticles for detection of cancer cells

Amino-modified magnetic nanoparticles were prepared by direct chemisorption of biocompatible d,l-lysine (DLL) on electrostatically stabilized magnetic nanoparticles with the aim to bind specific antibodies (Ab) able to detect cancer cells. The magnetic nanoparticles prepared by coprecipitation were stabilized in an acidic medium. A full optimization study of amino modification performed by UV/Vis spectroscopy and Dynamic Light Scattering measurement (DLS) confirmed an optimal DLL/Fe3O4 weight ratio of 2. The sample was subjected to complex characterizations using different techniques such as UV/Vis, FTIR and X-ray photoelectron spectroscopies (XPS) together with transmission electron microscopy and size/zeta potential measurements. While FTIR spectroscopy, UV/Vis spectroscopy and XPS confirmed the successful amino modification of Fe3O4 nanoparticles, a characterization using a vibrating sample magnetometer (VSM) indicated superparamagnetic behavior in all the prepared samples, suggesting that the coating process did not significantly affect the size and structure of the Fe3O4 nanoparticles. Magnetic nanoparticles with the optimal DLL content were conjugated with the M75 monoclonal antibody specific to carbonic anhydrase IX (CA IX), which is considered one of the best markers of tumor hypoxia and a prognostic indicator of cancer progression. The results demonstrate that all tested cell lines survived and even proliferated in the presence of amino-modified magnetic nanoparticles. Even the tubulin cytoskeletal structure was not disrupted after the exposure of cells to surface-modified magnetic nanoparticles. In contrast, internalization of the antibody-conjugated magnetic nanoparticles led to abrogation of the formation of long and extended microtubules. Finally, the finding supports the view that the M75 antibody conjugated to nanoparticles mediates their specific uptake and intracellular accumulation and that the antibody conjugated magnetic nanoparticles can be potentially used for the selective growth inhibition of CA IX-expressing cells.

Structure of amyloid aggregates of lysozyme from small-angle X-ray scattering data

The structure of filament amyloid aggregates of hen egg white lysozyme in water has been investigated by the small-angle X-ray scattering method. The experimental data are described by different cylindrical models, among which the best agreement is reached with the long helix model. A comparison of the results with the small-angle neutron scattering data reveals the influence of the heavy component of the solvent (a H2O/D2O mixture) on the structure of the filaments.

Thermal Properties of Magnetic Nanoparticles Modified With Polyethylene Glycol

Magnetic fluids used in biomedicine have to be biocompatible and therefore the magnetic nanoparticles are modified by different biocompatible materials. In this work the magnetic nanoparticles Fe3O4 sterically stabilized by sodium oleate were prepared by coprecipitation method. Consequently they were modified with polyethylene glycol (PEG) of different molecular weights and different PEG to magnetite Fe3O4 feed weight ratios varying from 0.01 to 30 to produce biocompatible magnetic fluids (MFPEG). The morphology was observed by scanning electron microscopy. The magnetic nanoparticles coated with PEG showed almost spherical shape for all studied systems of MFPEG. Differential scanning calorimetry (DSC) was used to study the adsorption of PEG on magnetic nanoparticles and to determine the maximal amount of PEG adsorbed on the magnetic nanoparticles. The increasing PEG molecular weight leads to the decrease in maximal PEG/Fe3O4 feed weight ratio. In vitro toxicity of the magnetic fluids using cells of skin cancer of mice B16 was tested with the aim to confirm the biocompatibility of the prepared magnetic fluids.

Biodistribution and In Vivo Anticancer Effects of Taxol Loaded Magnetic Nanospheres

Taxol (anticancer drug) loaded magnetic nanospheres were prepared and tested in vitro and in vivo in mice. Poly(D,L-lactide-co-glycolide) (PLGA) as polymer matrix for the encapsulation of the drug and magnetic (Fe3O4) particles was used. Pluronic F68 served as a stabilising agent of the polymeric nanospheres. The cytotoxicity of taxol loaded magnetic NPs suspensions towards B16 melanoma cells was investigated. Growth inhibitions of around 90% were reached in three days of exposition. Biodistribution of taxol administered in Cremophor-based injection formula as well as taxol loaded nanosphere compositions was determined in the plasma, selected organs and target tissue. The drug-loaded magnetically labeled nanospheres caused a reduction in tumor weight. A better result was achieved using the composition with higher magnetite/drug weight ratio than in the sample with the smaller ratio which is due to fact that the samples with higher magnetite content were trapped more effectively in target site (tumor) by the external field.

Degradation of BSA Coating on Magnetite Nanoparticles

Magnetic nanoparticles used in biomedicine have to be biocompatible what can be achieved by the modification of the magnetic particle surface with an appropriate biocompatible substance. In the work protein bovine serum albumin (BSA) was chosen to modify the surface of magnetite nanoparticles. BSA coated magnetite nanoparticles (MFBSA) with different feed weight ratios of BSA to the magnetite Fe3O4 were prepared and thermally characterized using thermogravimetric analysis.

Magnetic Fluids and Their Complex Systems

The presented chapter provides an overview of selected magnetic nanoparticle systems (magnetic fluids, magnetosomes, magnetoferritin and liquid crystals doped with magnetic particles) as the unique materials with potential utilization in the field of biological and biomedical applications as well as in the field of technology. The main idea for magnetic nanoparticles incorporating is the improvement of material properties and to achieve better conditions for a wide range of scientific disciplines such as magnetic hyperthermia, drug delivery, magneto-optics, power engineering and others.

Dynamic morphogenesis of dendritic structures formation in hen egg white lysozyme fibrils doped with magnetic nanoparticles

In this research, the dynamic process of aggregation that forms microflower morphology in solution of lysozyme amyloid fibrils doped with spherical or spindle-like magnetic nanoparticles during the process of drying as well as their final microstructures were investigated. The prepared lysozyme amyloid fibrils as well as their mixtures with in-lab synthesized magnetic particles, which were prepared by adding the nanoparticles to the fibrils solution after the process of fibrillation was done, were characterized using brightfield trans-illumination-mode optical microscope, atomic force microscopy (AFM) and scanning electron microscope (SEM). Brightfield optical imaging bases upon photoabsorptive property of the fibrils-nanoparticle composites clearly reveals the morphological features in microscale, and additionally, for the in vivo, live action of the time-dependent process of self-assembly of such composites composed of fibrillary structure incorporated with magnetic particles was optically elucidated at ambient temperature. Moreover, while results of AFM reveal delicate and peculiar association of fibrils with magnetic nanoparticles of different shapes, SEM images illustrate a stark difference in fine detailed final morphology of microstructures associated with spherical and spindle-like nanoparticles. Our results indicated that the interaction between fibrils solution and the nanoparticles commence right after mixing, the dynamic process of forming dendritic structure resembling microflower morphology is on the order of minutes, and its final structure is highly dependent on the shape of magnetic nanoparticles.