Synthetic and biogenic magnetite nanoparticles for tracking of stem cells and dendritic cells

Accurate delivery of cells to target organs is critical for success of cell-based therapies with stem cells or immune cells such as antigen-presenting dendritic cells (DC). Labeling with contrast agents before implantation provides a powerful means for monitoring cellular migration using magnetic resonance imaging (MRI). In this study, we investigated the uptake of fully synthesized or bacterial magnetic nanoparticles (MNPs) into hematopoietic Flt3⁺ stem cells and DC from mouse bone marrow. We show that (i) uptake of both synthetic and biogenic nanoparticles into cells endow magnetic activity and (ii) low numbers of MNP-loaded cells are readily detected by MRI.     

Synthesis of magnetic rhenium sulfide composite nanoparticles

Rhenium sulfide nanoparticles are associated with magnetic iron oxide through coprecipitation of iron salts with tetramethylammonium hydroxide. Sizes of the formed magnetic rhenium sulfide composite particles are in the range 5.5-12.5 nm. X-ray diffraction and energy-dispersive analysis of X-rays spectra demonstrate the coexistence of Fe₃O₄ and ReS₂ in the composite particle, which confirm the formation of the magnetic rhenium sulfide composite nanoparticles. The association of rhenium sulfide with iron oxide not only keeps electronic state and composition of the rhenium sulfide nanoparticles, but also introduces magnetism with the level of 24.1 emu g^-1 at 14 kOe. Surface modification with monocarboxyl-terminated poly(ethylene glycol) (MPEG-COOH) has the role of deaggregating the composite nanoparticles to be with average hydrodynamic size of 27.3 nm and improving the dispersion and the stability of the composite nanoparticles in water.     

Optimization of nanoparticle core size for magnetic particle imaging

Magnetic particle imaging (MPI) is a powerful new research and diagnostic imaging platform that is designed to image the amount and location of superparamagnetic nanoparticles in biological tissue. Here, we present mathematical modeling results that show how MPI sensitivity and spatial resolution both depend on the size of the nanoparticle core and its other physical properties, and how imaging performance can be effectively optimized through rational core design. Modeling is performed using the properties of magnetite cores, since these are readily produced with a controllable size that facilitates quantitative imaging. Results show that very low detection thresholds (of a few nanograms Fe₃O₄) and sub-millimeter spatial resolution are possible with MPI.     

Water-soluble magnetic nanoparticles with biologically active stabilizers

We present the results of the interaction of iron oxide nanoparticles with some biologically active surfactants, namely, oleic acid and cytotoxic alkanolamine derivatives. Physico-chemical properties, as magnetization, magnetite concentration and particle diameter, of the prepared magnetic samples were studied. The nanoparticle size of 11 nm for toluene magnetic fluid determined by TEM is in good agreement with the data obtained by the method of magnetogranulometry. In vitro cytotoxic effect of water-soluble nanoparticles with different iron oxide:oleic acid molar ratio were revealed against human fibrosarcoma and mouse hepatoma cells. In vivo results using a sarcoma mouse model showed observable antitumor action.     

Instant magnetic labeling of tumor cells by ultrasound in vitro

Magnetic labeling of living cells creates opportunities for numerous biomedical applications. Here we describe an instantly cell magnetic labeling method based on ultrasound. We present a detailed study on the ultrasound performance of a simple and efficient labeling protocol for H-22 cells in vitro. High frequency focus ultrasound was investigated as an alternative method to achieve instant cell labeling with the magnetic particles without the need for adjunct agents or initiating cell cultures. Mean diameter of 168 nm dextran-T40 coated superparamagnetic iron oxide (SPIO) nanoparticles were prepared by means of classical coprecipitation in solution in our laboratory. H-22 tumor cells suspended in phosphate-buffered saline (PBS, pH=7.2) were exposed to ultrasound at 1.37 MHz for up to 120 s in the presence of SPIOs. The cellular uptake of iron oxide nanoparticles was detected by prussion blue staining. The viability of cells was determined by a trypan blue exclusion test. At 2 W power and 60 s ultrasound exposure in presence of 410 μg/ml SPIOs, H-22 cell labeling efficiency reached 69.4±6.3% and the labeled cells exhibited an iron content of 10.38±2.43 pg per cell. Furthermore, 95.2±3.2% cells remained viable. The results indicated that the ultrasound protocol could be potentially applied to label cells with large-sized magnetic particles. We also calculated the shear stress at the 2 W power and 1.37 MHz used in experiments. The results showed that the shear stress threshold for ultrasonically induced H-22 cell reparable sonoporation was 697 Pa. These findings provide a quantitative guidance in designing ultrasound protocols for cell labeling.     

Carboxylated magnetic nanoparticles as MRI contrast agents: Relaxation measurements at different field strengths

At the moment the biomedical applications of magnetic fluids are the subject of intensive scientific interest. In the present work, magnetite nanoparticles (MNPs) were synthesized and stabilized in aqueous medium with different carboxylic compounds (citric acid (CA), polyacrylic acid (PAA), and sodium oleate (NaOA)), in order to prepare well stabilized magnetic fluids (MFs). The magnetic nanoparticles can be used in the magnetic resonance imaging (MRI) as contrast agents. Magnetic resonance relaxation measurements of the above MFs were performed at different field strengths (i.e., 0.47, 1.5 and 9.4 T) to reveal the field strength dependence of their magnetic responses, and to compare them with that of ferucarbotran, a well-known superparamagnetic contrast agent. The measurements showed characteristic differences between the tested magnetic fluids stabilized by carboxylic compounds and ferucarbotran. It is worthy of note that our magnetic fluids have the highest r2 relaxivities at the field strength of 1.5 T, where the most of the MRI works in worldwide.     

Preparation of size-controlled nanoparticles of magnetite

Samples of ferrofluids containing chemically stabilized nanoparticles of magnetite (Fe₃O₄) with tetramethylammonium hydroxide (TMAOH) were prepared by a direct reduction–precipitation method. The influences of aging time and temperature on the size and monodispersion characteristics of the produced nanoparticles were investigated. Transmission electron microscopy, powder X-ray diffraction, Fourier-transform infrared, and magnetization measurements with applied magnetic field up to 2 T were used to characterize the synthesized iron oxides. Raising the temperature of the synthesized material in autoclave affects positively the monodispersion of the nanoparticles, but it was not found to significantly influence the size itself of individual particles.     

Magnetic nanoparticles for application in cancer therapy

Magnetic particles play nowadays an important role in different technological areas with potential applications in fields such as electronics, energy and biomedicine. In this report we will focus on the hyperthermia properties of magnetite nanoparticles and the effect of several chemical/physical parameters on their heating properties. We will discuss about the need of searching new smaller magnetic systems in order to fulfill the required physical properties which allow treating tumoral tissues more efficiently by means of magnetically induced heat. Preliminary results will be shown about the effect of a biocompatible shell of core–shell magnetite NPs on the heating properties by application of a RF magnetic field.     

Ferrofluids of magnetic multicore nanoparticles for biomedical applications

For a variety of magnetically based biomedical applications, it is advantageous to use sedimentation stable suspensions of relatively large (d>20 nm) magnetic core-shell nanoparticles. Water-based suspensions of multicore nanoparticles were prepared by coating of the particles (synthesized by means of a modified alkaline precipitation method) with a carboxymethyldextran shell. The resulting ferrofluids were structurally and magnetically characterized. It was found that these fluids show a specific heating power of about 60 W/g (f=400 kHz, H=10 kA/m). This value was increased up to 330 W/g by a simple fractionation method based on centrifugation. Finally, the cellular uptake of the multicore nanoparticles was demonstrated.     

A comparative study of magnetic transferability of superparamagnetic nanoparticles

The aspect of magnetic transferability was established using an automated magnetic particle transfer workstation. Maghemite (γ-Fe₂O₃) nanoparticles were synthesized via conventional co-precipitation procedure. Their transferability was determined in addition to several commercial nanoparticles that ranged in diameter, surface functionality, and composition. Transmission and scanning electron micrographs and infrared spectrum, respectively, provided size and surface information on the synthesized particles for comparison to commercially available magnetic nanoparticles.     

Enhancing remote controlled heating characteristics in hydrophilic magnetite nanoparticles via facile co-precipitation

Citric acid coated magnetite nanoparticles were synthesized using a one-step and two-step co-precipitation method at different temperatures. The stability of the nanoparticles in aqueous media was compared. The magnetic heating characteristics in an alternating magnetic field were examined and specific absorption rates were determined. The nanoparticles were characterized by various techniques (Fourier transform infrared, UV spectrophotometry, thermogravimetric analysis, dynamic light scattering, transmission electron microscopy, X-ray diffraction and vibrating sample magnetometry). The temperature of synthesis and mode of functionalizing the particles affected their physical and magnetic properties. Higher temperatures led to increased specific absorption rates for both methods but more stable hydrophilic superparamagnetic nanoparticles were obtained in the one-step method.     

Investigations on magnetic particles prepared by cyclic growth

Magnetic iron oxide nanoparticles are promising tools for medical applications like hyperthermia or magnetic drug targeting. The relevant properties in these applications strongly depend on particle size and size distribution. In order to investigate the influence of mean size as well as size distribution, iron oxide powders from particles by a cyclic method based on “conventional” precipitation from Fe-salt solution were prepared. Increasing mean particle size with increasing number of cycles is confirmed by XRD. Magnetic parameters of the saturation hysteresis loop, hysteresis losses calculated from minor loops and switching field distributions are shown. A fractionation experiment on a fluid sample of particles prepared by 3 cycles was carried out in order to improve the hysteresis losses.     

Formation and properties of magnetic chains for 100 nm nanoparticles used in separations of molecules and cells

Optical observations of 100 nm metallic magnetic nanoparticles are used to study their magnetic field induced self assembly. Chains with lengths of tens of microns are observed to form within minutes at nanoparticle concentrations 10¹⁰/mL. Chain rotation and magnetophoresis are readily observed, and SEM reveals that long chains are not simple single particle filaments. Similar chains are detected for several 100 nm commercial bio-separation nanoparticles. We demonstrate the staged magnetic condensation of different types of nanoparticles into composite structures and show that magnetic chains bind to immuno-magnetically labeled cells, serving as temporary handles which allow novel magnetic cell manipulations.     

Characterization of magnetic nanoparticles by a modular Hall magnetometer

The magnetization of iron oxide, nickel and cobalt ferrite nanoparticles was successfully measured by using a modular magnetometer. The magnetometer was built by combining stand-alone equipments usually available at most laboratories such as a Gaussmeter, an electromagnet, a current source and a linear actuator. The magnetic moment sensitivity attained was about 10⁻⁶ Am² and the results were checked against measurements made on commercial VSM and SQUID magnetometers showing few percent errors.     

Analysis of high gradient magnetic field effects on distribution of nanoparticles injected into pulsatile blood stream

Magnetic nanoparticles are widely used in a wide range of applications including data storage materials, pharmaceutical industries as magnetic separation tools, anti-cancer drug carriers and micro valve applications. The purpose of the current study is to investigate the effect of a non-uniform magnetic field on bio-fluid (blood) with magnetic nanoparticles. The effect of particles as well as mass fraction on flow field and volume concentration is investigated. The governing non-linear differential equations, concentration and Navier-stokes are coupled with the magnetic field. To solve these equations, a finite volume based code is developed and utilized. A real pulsatile velocity is utilized as inlet boundary condition. This velocity is extracted from an actual experimental data. Three percent nanoparticles volume concentration, as drug carrier, is steadily injected in an unsteady, pulsatile and non-Newtonian flow. A power law model is considered for the blood viscosity. The results show that during the systole section of the heartbeat when the blood velocity increases, the magnetic nanoparticles near the magnetic source are washed away. This is due to the sudden increase of the hydrodynamic force, which overcomes the magnetic force. The probability of vein blockage increases when the blood velocity reduces during the diastole time. As nanoparticles velocity injection decreases (longer injection time) the wall shear stress (especially near the injection area) decreases and the retention time of the magnetic nanoparticles in the blood flow increases.     

Application of citrate-stabilized gold-coated ferric oxide composite nanoparticles for biological separations

Gold-coated magnetic nanoparticles were synthesized with size ranging from 15 to 40 nm using sodium citrates as the reducing agent. Oxidized magnetites (Fe₃O₄) fabricated by co-precipitation of Fe²⁺ and Fe³⁺ in strong alkaline solution were used as magnetic cores. The structures of gold (Au) shell and magnetic core (Au–Fe) were studied by transmission electron microscopy (TEM) image and energy dispersive spectroscopy (EDS) spectrum. Results from high-resolution X-ray diffraction (HR XRD) show that the Au–Fe oxide nanoparticles have a face-centered cubic shape with the crystalline faces of {1 1 1}. The Au-coated magnetic nanoparticles exhibited a surface plasmon resonance peak at 528 nm. The nanoparticles are well dispersed in distilled water. A 3000 G permanent magnet was successfully used for the separation of the functionalized nanoparticles. Magnetic properties of the nanoparticles were determined by magnetic force microscope (MFM) in nanometric resolution and vibrating sample magnetometer (VSM). Magnetic separation of biological molecules using Au-coated magnetic oxide composite nanoparticles was examined after attachment of protein immunoglobulin G (IgG) through electrostatic interactions. Using this method, separation was achieved with a maximum yield of 35% at an IgG concentration of 400 ng/ml.     

In vitro study of magnetic nanoparticles as the implant for implant assisted magnetic drug targeting

Magnetic nanoparticle (MNP) seeds were studied in vitro for use as an implant in implant assisted-magnetic drug targeting (IA-MDT). The magnetite seeds were captured in a porous polymer, mimicking capillary tissue, with an external magnetic field (70 mT) and then used subsequently to capture magnetic drug carrier particles (MDCPs) (0.87 μm diameter) with the same magnetic field. The effects of the MNP seed diameter (10, 50 and 100 nm), MNP seed concentration (0.25-2.0 mg/mL), and fluid velocity (0.03-0.15 cm/s) on the capture efficiency (CE) of both the MNP seeds and the MDCPs were studied. The CE of the 10 nm MNP seeds was never more than 30%, while those of the 50 and 100 nm MNP seeds was always greater than 80% and in many cases exceeded 90%. Only the MNP seed concentration affected its CE. The 10 nm MNP seeds did not increase the MDCP CE over that obtained in the absence of the MNP seeds, while the 50 and 100 nm MNP seeds increased significantly, typically by more than a factor of two. The 50 and 100 nm MNP seeds also exhibited similar abilities to capture the MDCPs, with the MDCP CE always increasing with decreasing fluid velocity and generally increasing with increasing MNP seed concentration. The MNP seed size, magnetic properties, and capacity to self-agglomerate and form clusters were key properties that make them a viable implant in IA-MDT.     

Synthesis and characterization of noscapine loaded magnetic polymeric nanoparticles

The delivery of noscapine therapies directly to the site of the tumor would ultimately allow higher concentrations of the drug to be delivered, and prolong circulation time in vivo to enhance the therapeutic outcome of this drug. Therefore, we sought to design magnetic based polymeric nanoparticles for the site directed delivery of noscapine to invasive tumors. We synthesized Fe₃O₄ nanoparticles with an average size of 10±2.5 nm. These Fe₃O₄ NPs were used to prepare noscapine loaded magnetic polymeric nanoparticles (NMNP) with an average size of 252±6.3 nm. Fourier transform infrared (FT-IR) spectroscopy showed the encapsulation of noscapine on the surface of the polymer matrix. The encapsulation of the Fe₃O₄ NPs on the surface of the polymer was confirmed by elemental analysis. We studied the drug loading efficiency of polylactide acid (PLLA) and poly (l-lactide acid-co-gylocolide) (PLGA) polymeric systems of various molecular weights. Our findings revealed that the molecular weight of the polymer plays a crucial role in the capacity of the drug loading on the polymer surface. Using a constant amount of polymer and Fe₃O₄ NPs, both PLLA and PLGA at lower molecule weights showed higher loading efficiencies for the drug on their surfaces.     

Enhancement of AC-losses of magnetic nanoparticles for heating applications

Aqueous ferrofluids of maghemite nanoparticles coated with carboxydextran were investigated with respect to their specific loss power (SLP) in dependence on frequency and field amplitude of magnetic AC-fields. In order to elucidate the effect of the size distribution on SLP fluid fractions with different mean particle core size were prepared by a magnetic separation procedure from the original ferrofluid. Structural characterisation by means of TEM and XRD as well as reconstruction of core size distributions from magnetisation curves reveals that the narrow size distributions of the fractions cover a range of mean core sizes from about 8 up to 20 nm. Spectra of the complex susceptibility were measured for a frequency range of 20 Hz to 1 MHz. From the imaginary part of the susceptibility the specific loss power is calculated in dependence on frequency. The results are compared with calorimetrical measurements performed in dependence on field amplitude up to 11 kA/m at 410 kHz. A very high specific loss power in the order of 400 W per gram maghemite was found at 410 kHz and 11 kA/m for the fluid fraction having the largest mean core diameter. A deviation from linear response behaviour is found for this sample showing a power law field dependence of the specific loss power SLPH^2.5. In addition to liquid suspensions measurements were performed with particles immobilised in mannitol or gel in order to elucidate the role of Brownian relaxation. The experimentally found dependence of SLP on the mean particle core diameter may be understood in the frame of the Debye dispersion model. Results are discussed with respect to applications of ferrofluids in RF-magnetic hyperthermia.     

Biocompatibility of various ferrite nanoparticles evaluated by in vitro cytotoxicity assays using HeLa cells

Magnetic nanoparticles for thermotherapy must be biocompatible and possess high thermal efficiency as heating elements. The biocompatibility of Fe₃O₄ (20-30 nm), ZnFe₂O₄ (15-30 nm) and NiFe₂O₄ (20-30 nm) nanoparticles was studied using a cytotoxicity colony formation assay and a cell viability assay. The Fe₃O₄ sample was found to be biocompatible on HeLa cells. While ZnFe₂O₄ and NiFe₂O₄ were non-toxic at low concentrations, HeLa cells exhibited cytotoxic effects when exposed to concentrations of 100 μg/ml nanoparticles.