Manipulation and tracking of superparamagnetic nanoparticles using MRI

The use of magnetic fields in magnetic resonance imaging (MRI) for the tracking and delivery of chemotherapeutics bound to superparamagnetic nanoparticles offers a promising method for the non-invasive treatment of inoperable tumours. Here we demonstrate that superparamagnetic magnetite nanoparticles fabricated by an easily scalable method can be driven and tracked in real time at high velocities in vitro using MRI hardware. Force balance calculations are consistent with the magnetic properties of individual 10 nm diameter particles that move collectively as micron sized agglomerates with hydrodynamic diameter similar to that inferred from zero-magnetic-field dynamic light scattering measurements.     

Transient magnetic birefringence for determining magnetic nanoparticle diameters in dense, highly light scattering media

The increasing use of biofunctionalized magnetic nanoparticles in biomedical applications calls for further development of characterization tools that allow for determining the interactions of the nanoparticles with the biological medium in situ. In cell-incubating conditions, for example, nanoparticles may aggregate and serum proteins adsorb on the particles, altering the nanoparticles' performance and their interaction with cell membranes. In this work we show that the aggregation of spherical magnetite nanoparticles can be detected with high sensitivity in dense, highly light scattering media by making use of magnetically induced birefringence. Moreover, the hydrodynamic particle diameter distribution of anisometric nanoparticle aggregates can be determined directly in these media by monitoring the relaxation time of the magnetically induced birefringence. As a proof of concept, we performed measurements on nanoparticles included in an agarose gel, which scatters light in a similar way as a more complex biological medium but where particle-matrix interactions are weak. Magnetite nanoparticles were separated by agarose gel electrophoresis and the hydrodynamic diameter distribution was determined in situ. For the different particle functionalizations and agarose concentrations tested, we could show that gel electrophoresis did not yield a complete separation of monomers and small aggregates, and that the electrophoretic mobility of the aggregates decreased linearly with the hydrodynamic diameter. Furthermore, the rotational particle diffusion was not clearly affected by nanoparticle-gel interactions. The possibility to detect nanoparticle aggregates and their hydrodynamic diameters in complex scattering media like cell tissue makes transient magnetic birefringence an interesting technique for biological applications.     

Bi-layered polymer–magnetite core/shell particles: synthesis and characterization

Polymer magnetic core particles receive growing attention due to these materials owing magnetic properties which are widely used in different applications. The prepared composite particles are characterized with different properties namely: a magnetic core, a hydrophobic first shell, and finally an external second hydrophilic shell. The present study describes a method for the preparation of bi-layered polymer magnetic core particles (diameter range is 50–150 nm). This method comprises several steps including the precipitation of the magnetic iron oxide, coating the magnetite with oleic acid, attaching the first polymer shell by miniemulsion polymerization and finally introducing hydrophilic surface properties by condensation polymerization. The first step is the formation of magnetite nanoparticles within a co-precipitation process using oleic acid as the stabilizing agent for magnetite. The second step is the encapsulation of magnetite into polyvinylbenzyl chloride particles by miniemulsion polymerization to form a magnetic core with a hydrophobic polymer shell. The hydrophobic shell is desired to protect magnetite nanoparticles against chemical attack. The third step is the coating of magnetic core hydrophobic polymer shell composites with a hydrophilic layer of polyethylene glycol by condensation polymerization. Regarding the miniemulsion polymerization the influence of the amount of water, the mixing intensity and the surfactant concentration were studied with respect to the formation of particles which can be further used in chemical engineering applications. The resulting magnetic polymer nanoparticles were characterized by particle size measurement, chemical stability, iron content, TEM, SEM, and IR.     

Magnetic properties of biosynthesized magnetite nanoparticles

Magnetic nanoparticles, which are unique because of both structural and functional elements, have various novel applications. The popularity and practicality of nanoparticle materials create a need for a synthesis method that produces quality particles in sizable quantities. This paper describes such a method, one that uses bacterial synthesis to create nanoparticles of magnetite. The thermophilic bacterial strain Thermoanaerobacter ethanolicus TOR-39 was incubated under anaerobic conditions at 65/spl deg/C for two weeks in aqueous solution containing Fe ions from a magnetite precursor (akaganeite). Magnetite particles formed outside of bacterial cells. We verified particle size and morphology by using dynamic light scattering, X-ray diffraction, and transmission electron microscopy. Average crystallite size was 45 nm. We characterized the magnetic properties by using a superconducting quantum interference device magnetometer; a saturation magnetization of 77 emu/g was observed at 5 K. These results are comparable to those for chemically synthesized magnetite nanoparticles.     

N-alkyl-polyethylenimine stabilized iron oxide nanoparticles as MRI visible transfection agents

An amphiphilic polymer, alkylated branched polyethylenimine (N-Alkyl-PEI), is synthesized and used for stabilization of hydrophobic superparamagnetic iron oxide (SPIO) nanocrystals in aqueous phase. Such composite particles are monodisperse without aggregation in physiological buffer as verified by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The nanocomposite system is capable of binding and delivering plasmid DNA for gene transfection while maintaining magnetic properties and biocompatibility. Transfection of cells showed that N-Alkyl-PEI2k stabilized magnetite nanoparticles were most effective in gene transfection comparing to unmodified PEI2k and PEI25k agents. Obvious MR signal darkening of transfected cells was observed under a clinical 3T MRI scanner. This multifunctional nanocomposite system provides a safe and efficient method for gene delivery with non-invasive imaging monitoring capability.     

Electrocodeposition of magnetic nickel matrix nanocomposites in a static magnetic field

The effect of an external magnetic field on the electrocodeposition of composites consisting of either Co or magnetite nanoparticles in a Ni matrix has been studied. An alkaline Ni pyrophosphate bath containing citrate was used. The magnetic particles were prepared by thermal decomposition (Co) or chemical precipitation (magnetite) and characterized by transmission electron microscopy, X-ray diffraction, dynamic light scattering, zeta potential and vibrating sample magnetometry measurements. The particle incorporation showed a distinct dependency on the orientation of an externally applied magnetic field. While the particle incorporation increased in a perpendicular field (perpendicular with regard to the electrode surface), it decreased in a parallel orientation. This result is explained with the dominating action of the magnetophoretic force. The structure and the properties of the Ni layers were significantly affected by the particle codeposition. A refinement of the Ni grains was found with increasing plating current density and as a result of the nanoparticle incorporation. The magnetic hardness and the Vickers microhardness of the films increased significantly due to the incorporation of the nanoparticles.     

Hydrothermal synthesis of magnetite nanoparticles via sequential formation of iron hydroxide precipitates

A novel method for preparing fine magnetite nanoparticles without using any additives and organic solvents has been developed. In this method, a sequential precipitates formation method, ferrous and ferric hydroxides are not coprecipitated but sequentially formed in an alkaline solution, and then the resulting suspension is subjected to a hydrothermal treatment. The obtained magnetite nanoparticles were characterised through scanning electron microscopy observation and X-ray diffraction analysis, and the particle size and magnetic properties were measured with a dynamic light scattering particle size analyser and a superconducting quantum interference device magnetometer, respectively. In order to prepare fine magnetite nanoparticles with a uniform size, both the formation sequence of ferrous and ferric hydroxide precipitates and the supersaturation of ferric hydroxide in the solution were essential. The ferromagnetic magnetite nanoparticles with a median size 8.5?nm were relatively easily obtained in the formation process in which a ferric sulphate solution was rapidly poured into a suspension of ferrous hydroxide particles prepared beforehand using ferric chloride and sodium hydroxide, whereas the median size of magnetite nanoparticles prepared via conventional coprecipitation route was 38.6?nm.     

Systematic study of bimodal suspensions of latex nanoparticles using dynamic light scattering

Determining the size of nanoparticles accurately, quickly and easily is becoming more and more important as the use of such particles increases. One of the common techniques for measuring the size of particles in suspension is dynamic light scattering (DLS). In principle, DLS is able to estimate the hydrodynamic particle diameter and its intensity-weighted distribution. However, the measured correlation function or power spectrum must be inverted to obtain this size distribution. The inversion is an ill-posed mathematical problem, and only under certain assumptions can the distribution be determined reliably. Suspensions containing bimodal (or multi-modal) particle size distributions are particularly challenging. This study reports on DLS measurements on a range of bimodal distributions of latex spheres with varying ratios of particle sizes. To determine the efficacy of different inversion techniques, the data has been analyzed both with the algorithms implemented in the DLS instrument’s proprietary analysis software and with other inversion routines based on simple analytical models of the particle size distribution. In addition, the results of the DLS analysis have been compared to scanning and transmission electron microscopy (SEM and TEM) measurements.     

Preparation of magnetic polymeric composite nanoparticles by seeded emulsion polymerization

Seeded emulsion polymerization was used to prepare magnetic polymeric composite nanoparticles (MPCNPs) with the aim to successfully encapsulate magnetite particles and to improve particle size distribution (PSD). Microscopical morphology and number-average diameter of hydrophilic magnetite particles (HMPs), magnetic seed latex nanoparticles (MSLNPs) and MPCNPs were observed and analyzed by transmission electron microscope (TEM). Weight-average diameter and PSD of MSLNPs and MPCNPs were also analyzed by TEM. Magnetic properties of MPCNPs were investigated by Vibrating Sample Magnetometry (VSM). The results showed that the encapsulation of magnetite particles was not complete by conventional emulsion polymerization but very successful by seeded emulsion polymerization, the resulted MPCNPs were nanoparticles with much narrower PSD than that of MSLNPs, and exhibited superparamagnetism and possessed a certain level of magnetic response.     

Asymmetric flow field-flow fractionation of superferrimagnetic iron oxide multicore nanoparticles

Magnetic nanoparticles are very useful for various medical applications where each application requires particles with specific magnetic properties. In this paper we describe the modification of the magnetic properties of magnetic multicore nanoparticles (MCNPs) by size dependent fractionation. This classification was carried out by means of asymmetric flow field-flow fractionation (AF4). A clear increase of the particle size with increasing elution time was confirmed by multi-angle laser light scattering coupled to the AF4 system, dynamic light scattering and Brownian diameters determined by magnetorelaxometry. In this way 16 fractions of particles with different hydrodynamic diameters, ranging between around 100 and 500?nm, were obtained. A high reproducibility of the method was confirmed by the comparison of the mean diameters of fractions of several fractionation runs under identical conditions. The hysteresis curves were measured by vibrating sample magnetometry. Starting from a coercivity of 1.41?kA?m(-1) for the original MCNPs the coercivity of the particles in the different fractions varied from 0.41 to 3.83?kA?m(-1). In our paper it is shown for the first time that fractions obtained from a broad size distributed MCNP fluid classified by AF4 show a strong correlation between hydrodynamic diameter and magnetic properties. Thus we state that AF4 is a suitable technology for reproducible size dependent classification of magnetic multicore nanoparticles suspended as ferrofluids.     

Size and surface effects on the MRI relaxivity of manganese ferrite nanoparticle contrast agents

Superparamagnetic MnFe2O4 nanocrystals of different sizes were synthesized in high-boiling ether solvent and transferred into water using three different approaches. First, we applied a ligand exchange in order to form a water soluble polymer shell. Second, the particles were embedded into an amphiphilic polymer shell. Third, the nanoparticles were embedded into large micelles formed by lipids. Although all approaches lead to effective negative contrast enhancement, we observed significant differences concerning the magnitude of this effect. The transverse relaxivity, in particular r2*, is greatly higher for the micellar system compared to the polymer-coated particles using same-sized nanoparticles. We also observed an increase in transverse relaxivities with increasing particle size for the polymer-coated nanocrystals. The results are qualitatively compared with theoretical models describing the dependence of relaxivity on the size of magnetic spheres.     

Impact of agglomeration on the relaxometric properties of paramagnetic ultra-small gadolinium oxide nanoparticles

Ultra-small gadolinium oxide nanoparticles (US-Gd(2)O(3)) are used to provide 'positive' contrast effects in magnetic resonance imaging (MRI), and are being considered for molecular and cellular imaging applications. However, these nanoparticles can aggregate over time in aqueous medium, as well as when internalized into cells. This study is aimed at measuring in vitro, in aqueous medium, the impact of aggregation on the relaxometric properties of paramagnetic US-Gd(2)O(3) particles. First, the nanoparticle core size as well as aggregation behaviour was assessed by HRTEM. DLS (hydrodynamic diameter) was used to measure the hydrodynamic diameter of nanoparticles and nanoaggregates. The relaxometric properties were measured by NMRD profiling, as well as with (1)H NMR relaxometers. Then, the positive contrast enhancement effect was assessed by using magnetic resonance scanners (at 1.5 and 7 T). At every magnetic field, the longitudinal relaxivity (r(1)) decreased upon agglomeration, while remaining high enough to provide positive contrast. On the other hand, the transverse relaxivity (r(2)) slightly decreased at 0.47 and 1.41 T, but it was enhanced at higher fields (7 and 11.7 T) upon agglomeration. All NMRD profiles revealed a characteristic relaxivity peak in the range 60-100 MHz, suggesting the possibility to use US-Gd(2)O(3) as an efficient 'positive-T(1)' contrast agent at clinical magnetic fields (1-3 T), in spite of aggregation.     

Structure and Magnetic Properties of Polymer Microspheres Filled with Magnetite Nanoparticles

The structure and magnetic properties of collagen microspheres filled with magnetite nanoparticles are studied. The average interparticle separation in the polymer matrix and the size of magnetite nanoparticles before and after the introduction of the nanoparticles into the matrix are determined using electron microscopy. The magnetization curve of the microspheres has a superparamagnetic character. The magnetite nanoparticles undergo no aggregation during the synthesis of microspheres and are evenly distributed over the matrix. The magnetic susceptibility data for magnetic polymer microspheres of different diameters suggest that, at small diameters (<300 m), all of the nanoparticles, aligned in chains, contribute to magnetization; at large diameters, some of the chains give way to clusters, the chains are shorter, and, accordingly, the susceptibility is lower.     

Biological colloid engineering: Self-assembly of dipolar ferromagnetic chains in a functionalized biogenic ferrofluid

We have studied the dynamic behavior of nanoparticles in ferrofluids consisting of single-domain, biogenic magnetite (Fe(3)O(4)) isolated from Magnetospirillum magnetotacticum (MS-1). Although dipolar chains form in magnetic colloids in zero applied field, when dried upon substrates, the solvent front disorders nanoparticle aggregation. Using avidin-biotin functionalization of the particles and substrate, we generated self-assembled, linear chain motifs that resist solvent front disruption in zero-field. The engineered self-assembly process we describe here provides an approach for the creation of ordered magnetic structures that could impact fields ranging from micro-electro-mechanical systems development to magnetic imaging of biological structures.     

Parametric characterizations in superparamagnetic latex

The effect of synthesis parameters on the production of superparamagnetic latex, which are magnetite nanoparticles covered with a poly(methyl methacrylate) layer, were studied. The synthesis method was based on the developed route of emulsifier-free emulsion polymerization. Under this study, effects of the monomer and initiator concentrations, the amount of magnetic sol, the stirring rate and the adding rate of the magnetic sol on the properties of synthesized latexes were investigated. The characterizations were performed by a high resolution transmission electron microscopy, a dynamic light scattering, a vibrating sample magnetometer and a gel permeation chromatography. The results showed that the monomer concentration was found to be the most effective parameter on latex stability. As the initiator amount and the stirring rate increased, saturation magnetization and average molecular weight decreased due to the reactions occurring between surfaces of magnetite nanoparticles and initiator fragments. On increasing amount of magnetic sol, the saturation magnetization and polymer molecular weight increased but the size of nanospheres was unchanged because of the ions in magnetic sol. It was seen that the desired size and magnetic properties of the latex could be obtained since the parameters were found to have substantial impact on their properties.     

Microwave properties of polymer composites containing combinations of micro- and nano-sized magnetic fillers

We investigated the microwave absorbing properties of composite bulk samples with nanostructured and micron-sized fillers. As magnetic fillers we used magnetite powder (Fe3O4 with low magnetocrystalline anisotropy) and strontium hexaferrite (SrFe12O9 with high magnetocrystalline anisotropy). The dielectric matrix consisted of silicone rubber. The average particle size was 30 nm for the magnetite powder and 6 micro/m for the strontium hexaferrite powder. The micron-sized SrFe12O19 powder was prepared using a solid-state reaction. We investigated the influence of the filler concentration and the filler ratio (Fe3O4/SrFe12O19) in the polymer matrix on the microwave absorption in a large frequency range (1 / 18 GHz). The results obtained showed that the highly anisotropic particles become centers of clusterification and the small magnetite particles form magnetic balls with different diameter depending on the concentration. The effect of adding micron-sized SrFe12O19 to the nanosized Fe3O4 filler in composites absorbing structures has to do with the ferromagnetic resonance (FMR) shifting to the higher frequencies due to the changes in the ferrite filler's properties induced by the presence of a magnetic material with high magnetocrystalline anisotropy. The two-component filler possesses new values of the saturation magnetization and of the anisotropy constant, differing from those of both SrFe12O1919 and Fe3O4, which leads to a rise in the effective anisotropy field. The results demonstrate the possibility to vary the composite's absorption characteristics in a controlled manner by way of introducing a second magnetic material.     

A simple synthesis of amine-derivatised superparamagnetic iron oxide nanoparticles for bioapplications

Adsorption of 3-aminopropyltriethoxysilane (APTS) on magnetite nanoparticles during its formation has been investigated to optimise the preparation of stable aqueous dispersion of amine derivatised magnetite nanoparticles. APTS adsorbs chemically on the surface of magnetite particle modifying its surface which is evident from thermal and C, H, N analysis. The variation of particle size has been observed with change of APTS concentration. X-ray diffractogram shows the formation of pure inverse spinel phase magnetite with average crystallite size 7 nm when equimolar (Fe₃O₄: APTS = 1:1) quantity of APTS was used during its synthesis. The presence of free surface –NH₂ groups and Fe–O–Si bonds was observed by FTIR. Raman spectrum further confirms the presence of surface –NH₂ groups. Transmission electron microscopy shows formation of particles of average size between 7 nm and 12 nm. The effective hydrodynamic diameter of the APTS coated particle agglomerates is 45.8 nm in stable aqueous colloidal dispersion, which is evident from photon correlation spectroscopy. VSM measurements at room temperature of both silanised and unsilanised magnetite shows their superparamagnetic nature with saturation magnetisation 41 e.m.u/g and 56 e.m.u/g, respectively. Avidin has been immobilised on the surface through glutaraldehyde, which demonstrates the possibility of the synthesised material to be used in protein immobilisation to form bioactive magnetic particles.     

Synthesis and characterization of ultrafine poly(vinylalcohol phosphate) coated magnetite nanoparticles

Nanosized magnetite (Fe3O4) particles showing superparamagnetism at room temperature have been prepared by controlled coprecipitation of Fe2+ and Fe3+ in presence of highly hydrophilic poly(vinylalcohol phosphate)(PVAP). The impact of polymer concentration on particle size, size distribution, colloidal stability, and magnetic property has been extensively studied. The aqueous suspension of magnetite, prepared using 1% PVAP solution is stable for four weeks at pH 5-8. X-ray diffractograms show the formation of nanocrystalline inverse spinel phase magnetite. Transmission Electron Microscopy confirmed well dispersed cubic magnetite particles of size of about 5.8 nm. Dynamic Light Scattering measurement shows narrow distribution of hydrodynamic size of particle aggregates. Infrared spectra of samples show strong Fe--O--P bond on the oxide surface. UV-visible studies show aqueous dispersion of magnetite formed by using 1% PVAP solution is stable at least for four weeks without any detoriation of particle size. Magnetization measurements at room temperature show superparamagnetic nature of polymer coated magnetite nanoparticles.     

Synthesis and characterisation of magnetite nanoparticles using gelatin and starch as capping agents

Nanoparticles of magnetite passivated with gelatin and starch were synthesised using a co‐precipitation technique. The nanoparticles were characterised using ultraviolet–visible (UV–vis), dynamic light scattering (DLS), Zeta potential, transmission electron microscope (TEM), X‐ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). The UV–vis spectra showed characteristic surface plasmon resonance of magnetite nanoparticles. The DLS results showed the nanoparticles to have average hydrodynamic diameters of 138 ± 2 and 283 ± 21 nm for particles passivated with gelatin and starch, respectively. The stability in a colloidal solution was greater in nanoparticles passivated with gelatin than nanoparticles obtained with starch, as can be seen by their Zeta potential value (−31 ± 2 and −16 ± 0.5 mV, respectively). According to the TEM evaluation, the use of gelatin allowed to obtain nanoparticles with a spherical morphology and an average size of 10 ± 2 nm. However, when using starch the nanoparticles exhibited diverse morphologies with an average size of 25 ± 7 nm. The XRD results confirmed the crystalline structure of the samples, which showed crystallite sizes of 14.90 and 24.43 nm for nanoparticles passivated with gelatin and starch, respectively. FTIR analysis proved the establishment of interactions between functional groups of biopolymers and magnetite nanoparticles.Inspec keywords: crystallites, nanofabrication, ultraviolet spectra, gelatin, surface plasmon resonance, transmission electron microscopy, scanning electron microscopy, visible spectra, X‐ray diffraction, iron compounds, electrokinetic effects, particle size, colloids, nanoparticles, nanomedicine, precipitation (physical chemistry), light scattering, magnetic particles, Fourier transform infrared spectra, nanomagnetics, filled polymers, nanocompositesOther keywords: magnetite nanoparticles, gelatin, starch, characteristic surface plasmon resonance, capping agents, passivation, co‐precipitation technique, ultraviolet–visible spectra, zeta potential value, dynamic light scattering, DLS, transmission electron microscopy, TEM, X‐ray diffraction, XRD, Fourier transform infrared spectroscopy, FTIR, surface plasmon resonance, hydrodynamic diameters, colloidal solution, spherical morphology, crystalline structure, crystallite size, biopolymers, Fe₂ O₃      

Pullulan acetate coated magnetite nanoparticles for hyper-thermia: Preparation, characterization and in vitro experiments

Amphipathic polymer pullulan acetate (PA)-coated magnetic nanoparticles were prepared and characterized by various physicochemical means. The cytotoxicity and cellular uptake of the magnetic nanoparticles were examined. The hyperthermic effect of the magnetic nanoparticles on tumor cells was evaluated. Transmission electron microscopy (TEM) showed that the PA coated magnetic nanoparticles (PAMNs) had spherical morphology. Dynamic light scattering (DLS) showed that the size distribution of PAMNs was unimodal,with an average diameter of 25.8 nm ± 6.1 nm. The presence of the adsorbed layer of PA on the magnetite surface was confirmed by Fourier transform infrared (FTIR) spectroscopy. Magnetic measurements revealed that the saturation magnetization of the PAMNs reached 51.9 emu/g and the nanoparticles were superparamagnetic. Thermogravimetric analysis (TGA) showed that the Fe₃O₄ particles constituted 75 wt% of the PAMNs. The PAMNs had good heating properties in an alternating magnetic field. Cytotoxicity assay showed that PAMNs exhibited no significant cytotoxicity against L929 cells. TEM results showed that a large number of PAMNs were internalized into KB cells. PAMNs have good hyperthermia effect on KB cells in vitro by magnetic field induced hyperthermia. These novel magnetic nanoparticles have great potential as magnetic hyperthermia mediators.