Heat dissipation in Sm3+ and Zn2+ co-substituted magnetite (Zn0.1SmxFe2.9-xO4) nanoparticles coated with citric acid and pluronic F127 for hyperthermia application.

In this work, Sm3+ and Zn2+ co-substituted magnetite Zn0.1SmxFe2.9-xO4 (x = 0.0, 0.01, 0.02, 0.03, 0.04 and 0.05) nanoparticles, have been prepared via co-precipitation method and were electrostatically and sterically stabilized by citric acid and pluronic F127 coatings. The coated nanoparticles were well dispersed in an aqueous solution (pH 5.5). Magnetic and structural properties of the nanoparticles and their ferrofluids were studied by different methods. XRD studies illustrated that all as-prepared nanoparticles have a single phase spinel structure, with lattice constants affected by samarium cations substitution. The temperature dependence of the magnetization showed that Curie temperatures of the uncoated samples monotonically increased from 430 to 480 °C as Sm3+ content increased, due to increase in A-B super-exchange interactions. Room temperature magnetic measurements exhibited a decrease in saturation magnetization of the uncoated samples from 98.8 to 71.9 emu/g as the Sm3+ content increased, which is attributed to substitution of Sm3+ (1.5 µB) ions for Fe3+ (5 µB) ones in B sublattices. FTIR spectra confirmed that Sm3+ substituted Zn0.1SmxFe2.9-xO4 nanoparticles were coated with both citric acid and pluronic F127 properly. The mean particle size of the coated nanoparticles was 40 nm. Calorimetric measurements showed that the maximum SLP and ILP values obtained for Sm3+ substituted nanoparticles were 259 W/g and 3.49 nHm2/kg (1.08 mg/ml, measured at f = 290 kHz and H = 16kA/m), respectively, that are related to the sample with x = 0.01. Magnetic measurements revealed coercivity, which indicated that hysteresis loss may represent a substantial portion in heat generation. Our results show that these ferrofluids are potential candidates for magnetic hyperthermia applications.

Surface-modified magnetite nanoparticles affect lysozyme amyloid fibrillization.

BACKGROUND: The surface of nanoparticles (NPs) is an important factor affecting the process of poly/peptides' amyloid aggregation. We have investigated the in vitro effect of trisodium citrate (TC), gum arabic (GA) and citric acid (CA) surface-modified magnetite nanoparticles (COAT-MNPs) on hen egg-white lysozyme (HEWL) amyloid fibrillization and mature HEWL fibrils. METHODS: Dynamic light scattering (DLS) was used to characterize the physico-chemical properties of studied COAT-MNPs and determine the adsorption potential of their surface towards HEWL. The anti-amyloid properties were studied using thioflavin T (ThT) and tryptophan (Trp) intrinsic fluorescence assays, and atomic force microscopy (AFM). The morphology of amyloid aggregates was analyzed using Gwyddion software. The cytotoxicity of COAT-MNPs was determined utilizing Trypan blue (TB) assay. RESULTS: Agents used for surface modification affect the COAT-MNPs physico-chemical properties and modulate their anti-amyloid potential. The results from ThT and intrinsic fluorescence showed that the inhibitory activities result from the more favorable interactions of COAT-MNPs with early pre-amyloid species, presumably reducing nuclei and oligomers formation necessary for amyloid fibrillization. COAT-MNPs also possess destroying potential, which is presumably caused by the interaction with hydrophobic residues of the fibrils, resulting in the interruption of an interface between ß-sheets stabilizing the amyloid fibrils. CONCLUSION: COAT-MNPs were able to inhibit HEWL fibrillization and destroy mature fibrils with different efficacy depending on their properties, TC-MNPs being the most potent nanoparticles. GENERAL SIGNIFICANCE: The study reports findings regarding the general impact of nanoparticles' surface modifications on the amyloid aggregation of proteins.

Challenges and recommendations for magnetic hyperthermia characterization measurements.

PURPOSE: The localized heating of magnetic nanoparticles (MNPs) via the application of time-varying magnetic fields - a process known as magnetic field hyperthermia (MFH) - can greatly enhance existing options for cancer treatment; but for broad clinical uptake its optimization, reproducibility and safety must be comprehensively proven. As part of this effort, the quantification of MNP heating - characterized by the specific loss power (SLP), measured in W/g, or by the intrinsic loss power (ILP), in Hm2/kg - is frequently reported. However, in SLP/ILP measurements to date, the apparatus, the analysis techniques and the field conditions used by different researchers have varied greatly, leading to questions as to the reproducibility of the measurements. MATERIALS AND METHODS: An interlaboratory study (across N = 21 European sites) of calorimetry measurements that constitutes a snapshot of the current state-of-the-art within the MFH community has been undertaken. Identical samples of two stable nanoparticle systems were distributed to all participating laboratories. Raw measurement data as well as the results of in-house analysis techniques were collected along with details of the measurement apparatus used. Raw measurement data was further reanalyzed by universal application of the corrected-slope method to examine relative influences of apparatus and results processing. RESULTS: The data show that although there is very good intralaboratory repeatability, the overall interlaboratory measurement accuracy is poor, with the consolidated ILP data having standard deviations on the mean of ca. ± 30% to ± 40%. There is a strong systematic component to the uncertainties, and a clear rank correlation between the measuring laboratory and the ILP. Both of these are indications of a current lack of normalization in this field. A number of possible sources of systematic uncertainties are identified, and means determined to alleviate or minimize them. However, no single dominant factor was identified, and significant work remains to ascertain and remove the remaining uncertainty sources. CONCLUSION: We conclude that the study reveals a current lack of harmonization in MFH characterization of MNPs, and highlights the growing need for standardized, quantitative characterization techniques for this emerging medical technology.

Weak Polyampholytes at the Interface of Magnetic Nanocarriers: A Facile Catch-and-Release Platform for Dyes.

We present a platform of charge-invertible core-shell hybrid particles for the selective and reversible adsorption of small charged molecules as model systems. The herein employed carrier systems consist of an iron oxide core coated with different pH-responsive polyampholytes which exhibit varying surface charge depending on the surrounding pH value. The resulting materials were used for electrostatically mediated catch-and-release experiments of either cationic or anionic dyes with the perspective to allow the pH-dependent magnetically guided transport of suitable cargo. The use of three different polyampholyte coatings (poly(2-(imidazol-1-yl)acrylic acid) (PImAA), poly(dehydroalanine) (PDha), and poly(N,N-diallylglutamate) (PDAGA)) enables a deeper understanding about how the surface net charge in combination with the charge and charge density of any cargo influences such processes. The size, surface charge, and aggregation behavior of the herein described particles were investigated via dynamic light scattering (DLS), transmission electron microscopy (TEM), and pH-dependent ζ-potential measurements, whereas adsorption and release studies were investigated via UV-vis.

Fractionation of Magnetic Microspheres in a Microfluidic Spiral: Interplay between Magnetic and Hydrodynamic Forces.

Magnetic forces and curvature-induced hydrodynamic drag have both been studied and employed in continuous microfluidic particle separation and enrichment schemes. Here we combine the two. We investigate consequences of applying an outwardly directed magnetic force to a dilute suspension of magnetic microspheres circulating in a spiral microfluidic channel. This force is realized with an array of permanent magnets arranged to produce a magnetic field with octupolar symmetry about the spiral axis. At low flow rates particles cluster around an apparent streamline of the flow near the outer wall of the turn. At high flow rates this equilibrium is disrupted by the induced secondary (Dean) flow and a new equilibrium is established near the inner wall of the turn. A model incorporating key forces involved in establishing these equilibria is described, and is used to extract quantitative information about the magnitude of local Dean drag forces from experimental data. Steady-state fractionation of suspensions by particle size under the combined influence of magnetic and hydrodynamic forces is demonstrated. Extensions of this work could lead to new continuous microscale particle sorting and enrichment processes with improved fidelity and specificity.

Preparation of Core-Shell Hybrid Materials by Producing a Protein Corona Around Magnetic Nanoparticles.

Nanoparticles experience increasing interest for a variety of medical and pharmaceutical applications. When exposing nanomaterials, e.g., magnetic iron oxide nanoparticles (MNP), to human blood, a protein corona consisting of various components is formed immediately. The composition of the corona as well as its amount bound to the particle surface is dependent on different factors, e.g., particle size and surface charge. The actual composition of the formed protein corona might be of major importance for cellular uptake of magnetic nanoparticles. The aim of the present study was to analyze the formation of the protein corona during in vitro serum incubation in dependency of incubation time and temperature. For this, MNP with different shells were incubated in fetal calf serum (FCS, serving as protein source) within a water bath for a defined time and at a defined temperature. Before and after incubation the particles were characterized by a variety of methods. It was found that immediately (seconds) after contact of MNP and FCS, a protein corona is formed on the surface of MNP. This formation led to an increase of particle size and a slight agglomeration of the particles, which was relatively constant during the first minutes of incubation. A longer incubation (from hours to days) resulted in a stronger agglomeration of the FCS incubated MNP. Quantitative analysis (gel electrophoresis) of serum-incubated particles revealed a relatively constant amount of bound proteins during the first minutes of serum incubation. After a longer incubation (>20 min), a considerably higher amount of surface proteins was determined for incubation temperatures below 40 °C. For incubation temperatures above 50 °C, the influence of time was less significant which might be attributed to denaturation of proteins during incubation. Overall, analysis of the molecular weight distribution of proteins found in the corona revealed a clear influence of incubation time and temperature on corona composition.

Magnetic core-shell fluorescent pH ratiometric nanosensor using a Stöber coating method.

We describe the use of a modified Stöber method for coating maghemite (γ-Fe(2)O(3)) nanocrystals with silica shells in order to built magnetic fluorescent sensor nanoparticles in the 50-70nm diameter range. In detail, the magnetic cores were coated by two successive silica shells embedding two fluorophores (two different silylated dye derivatives), which allows for ratiometric pH-measurements in the pH range 5-8. Silica coated magnetic nanoparticles were prepared using maghemite nanocrystals as cores (5-10nm in diameter) coated by tetraethoxyorthosilicate via hydrolysis/condensation in ethanol, catalyzed by ammonia. In the inner shell was covalently attached a sulforhodamine B, which was used as a reference dye; while a pH-sensitive fluorescein was incorporated into the outer shell. Once synthesized, the particles were characterized in terms of morphology, size, composition and magnetization, using dynamic light scattering (DLS), transmission electron microscopy (TEM), X-ray diffraction (XRD) and vibrating sample magnetometry (VSM). TEM analysis showed the nanoparticles to be very uniform in size. Wide-angle X-ray diffractograms showed, for uncoated as well as coated nanoparticles, typical peaks for the spinel structure of maghemite at the same diffraction angle, with no structural changes after coating. When using VSM, we obtained the magnetization curves of the resulting nanoparticles and the typical magnetization parameters as saturation magnetization (M(s)), coercivity (H(c)), and remanent magnetization (M(r)). The dual-dye doped magnetic-silica nanoparticles showed a satisfactory magnetization that could be suitable for nanoparticle separation and localized concentration of them. Changes in fluorescence intensity of the pH indicator in the different pH buffered solutions were observed within few seconds indicating an easy accessibility of the embedded dye by protons through the pores of the silica shell. The relationship between the ratio in fluorescence (sensor/reference dyes) and pH was adjusted to a sigmoidal fit using a Boltzmann type equation. Finally, the proposed method was statistically validated against a reference procedure using samples of water and physiological buffer with 2% (w/v) of horse serum added, indicating that there are no significant statistical differences at a 95% confidence level.

Investigation of water and ice by ac impedance using electrochemical properties cup.

Water and ice were investigated by ac impedance with the electrochemical properties cup in an effort to develop an in situ instrument for water characterization. In liquid water, the impedance modulus decreased with the increase in charge carriers. In the ice, the impedance measurements were characterized by the dielectric relaxation and its corresponding activation energy. The activation energy of 0.400 eV was determined for pure ice. With ice containing Cl(-) anions, the activation energy was 0.24 eV. H(+) and OH(-) doped ice has the lowest activation energy for dielectric relaxation. Results from previous works are similar to the results reported in this study.

Activation of calcium currents in cardiac myocytes by empty beta-adrenoceptors.

BACKGROUND: The cardiac calcium channel is known to be modulated by catecholamines via beta-adrenoceptors acting through intermediary GTP-binding regulatory proteins (G proteins). In biochemical studies on isolated membranes and reconstituted systems, it has been demonstrated that various G protein-coupled receptors, including beta-adrenoceptors, can activate G proteins and also intracellular second messengers like cyclic AMP (cAMP) even in the absence of an agonist and that antagonists can block this empty receptor action. We examined electrophysiologically whether agonist-free beta-adrenoceptors can modulate L-type calcium currents (ICa) in intact cardiac myocytes. METHODS AND RESULTS: Cardiomyocytes were isolated from ventricles of guinea pig and human hearts and from human right atrial appendage. The patch-clamp technique was applied in the single electrode mode to measure whole-cell ICa. Modulation of calcium currents by beta-adrenoceptor antagonists, without addition of an agonist, was studied in the absence and presence of the direct adenylyl cyclase activator forskolin and the cAMP analog adenosine cyclic 3',5'-monophosphorothioate (Sp-cAMPS). In the presence of forskolin (0.5 mumol/L), an agent known to sensitize the adenylyl cyclase signal transduction system for receptor regulation, addition of the beta 1-selective antagonist atenolol and the nonselective antagonist propranolol (but not of the beta 2-selective antagonist ICI 118,551) caused a marked reduction of ICa in a concentration-dependent and stereoselective manner. The inhibitory effect of atenolol was reversible after washing out and was found to be half maximal and maximal (50% reduction) at about 50 and 300 nmol/L, respectively. In the absence of forskolin, inhibition of ICa by atenolol was markedly less (18% at 10 mumol/L atenolol). Finally, in contrast to forskolin-stimulated currents, atenolol (1 mumol/L) did not reduce calcium currents activated by the protein kinase A activator Sp-cAMPS (0.1 mmol/L), causing by itself a similar increase in calcium currents as forskolin. CONCLUSIONS: In isolated guinea pig and human cardiomyocytes, agonist-free beta-adrenoceptors are functionally active and can stimulate L-type calcium currents, an effect blocked by receptor-specific antagonists.