Classification of Magnetic Nanoparticle Systems--Synthesis, Standardization and Analysis Methods in the NanoMag Project.

This study presents classification of different magnetic single- and multi-core particle systems using their measured dynamic magnetic properties together with their nanocrystal and particle sizes. The dynamic magnetic properties are measured with AC (dynamical) susceptometry and magnetorelaxometry and the size parameters are determined from electron microscopy and dynamic light scattering. Using these methods, we also show that the nanocrystal size and particle morphology determines the dynamic magnetic properties for both single- and multi-core particles. The presented results are obtained from the four year EU NMP FP7 project, NanoMag, which is focused on standardization of analysis methods for magnetic nanoparticles.

Polymer/Iron Oxide Nanoparticle Composites--A Straight Forward and Scalable Synthesis Approach.

Magnetic nanoparticle systems can be divided into single-core nanoparticles (with only one magnetic core per particle) and magnetic multi-core nanoparticles (with several magnetic cores per particle). Here, we report multi-core nanoparticle synthesis based on a controlled precipitation process within a well-defined oil in water emulsion to trap the superparamagnetic iron oxide nanoparticles (SPION) in a range of polymer matrices of choice, such as poly(styrene), poly(lactid acid), poly(methyl methacrylate), and poly(caprolactone). Multi-core particles were obtained within the Z-average size range of 130 to 340 nm. With the aim to combine the fast room temperature magnetic relaxation of small individual cores with high magnetization of the ensemble of SPIONs, we used small (<10 nm) core nanoparticles. The performed synthesis is highly flexible with respect to the choice of polymer and SPION loading and gives rise to multi-core particles with interesting magnetic properties and magnetic resonance imaging (MRI) contrast efficacy.

Keeping it real: The importance of material characterization in nanotoxicology.

Nanomaterials are small and the small size and corresponding large surface area of nanomaterials confers specific properties, making these materials desirable for various applications, not least in medicine. However, it is pertinent to ask whether size is the only property that matters for the desirable or detrimental effects of nanomaterials? Indeed, it is important to know not only what the material looks like, but also what it is made of, as well as how the material interacts with its biological surroundings. It has been suggested that guidelines should be implemented on the types of information required in terms of physicochemical characterization of nanomaterials for toxicological studies in order to improve the quality and relevance of the published results. This is certainly a key issue, but it is important to keep in mind that material characterization should be fit-for-purpose, that is, the information gathered should be relevant for the end-points being studied.

Freshwater dispersion stability of PAA-stabilised cerium oxide nanoparticles and toxicity towards Pseudokirchneriella subcapitata.

An aqueous dispersion of poly (acrylic acid)-stabilised cerium oxide (CeO2) nanoparticles (PAA-CeO2) was evaluated for its stability in a range of freshwater ecotoxicity media (MHRW, TG 201 and M7), with and without natural organic matter (NOM). In a 15 day dispersion stability study, PAA-CeO2 did not undergo significant aggregation in any media type. Zeta potential varied between media types and was influenced by PAA-CeO2 concentration, but remained constant over 15 days. NOM had no influence on PAA-CeO2 aggregation or zeta potential. The ecotoxicity of the PAA-CeO2 dispersion was investigated in 72 h algal growth inhibition tests using the freshwater microalgae Pseudokirchneriella subcapitata. PAA-CeO2 EC50 values for growth inhibition (GI; 0.024 mg/L) were 2-3 orders of magnitude lower than pristine CeO2 EC50 values reported in the literature. The concentration of dissolved cerium (Ce(3+)/Ce(4+)) in PAA-CeO2 exposure suspensions was very low, ranging between 0.5 and 5.6 µg/L. Free PAA concentration in the exposure solutions (0.0096-0.0384 mg/L) was significantly lower than the EC10 growth inhibition (47.7 mg/L) value of pure PAA, indicating that free PAA did not contribute to the observed toxicity. Elemental analysis indicated that up to 38% of the total Cerium becomes directly associated with the algal cells during the 72 h exposure. TOF-SIMS analysis of algal cell wall compounds indicated three different modes of action, including a significant oxidative stress response to PAA-CeO2 exposure. In contrast to pristine CeO2 nanoparticles, which rapidly aggregate in standard ecotoxicity media, PAA-stabilised CeO2 nanoparticles remain dispersed and available to water column species. Interaction of PAA with cell wall components, which could be responsible for the observed biomarker alterations, could not be excluded. This study indicates that the increased dispersion stability of PAA-CeO2 leads to an increase in toxicity compared to pristine non-stabilised forms.

Enzymatic 'stripping' and degradation of PEGylated carbon nanotubes.

Single-walled carbon nanotubes (SWCNTs) coated or functionalized with PEG chains of different molecular weight were assessed for their propensity to undergo biodegradation under in vitro conditions using recombinant myeloperoxidase (MPO) or ex vivo using freshly isolated primary human neutrophils. Our findings suggest that under natural conditions, a combined process of 'stripping' (i.e., defunctionalization) and biodegradation of PEG-SWCNTs might occur and that PEG-SWCNTs are a promising--and degradable--nanomedicine vector.

Biodegradation of single-walled carbon nanotubes by eosinophil peroxidase.

Eosinophil peroxidase (EPO) is one of the major oxidant-producing enzymes during inflammatory states in the human lung. The degradation of single-walled carbon nanotubes (SWCNTs) upon incubation with human EPO and H2O2 is reported. Biodegradation of SWCNTs is higher in the presence of NaBr, but neither EPO alone nor H2O2 alone caused the degradation of nanotubes. Molecular modeling reveals two binding sites for SWCNTs on EPO, one located at the proximal side (same side as the catalytic site) and the other on the distal side of EPO. The oxidized groups on SWCNTs in both cases are stabilized by electrostatic interactions with positively charged residues. Biodegradation of SWCNTs can also be executed in an ex vivo culture system using primary murine eosinophils stimulated to undergo degranulation. Biodegradation is proven by a range of methods including transmission electron microscopy, UV-visible-NIR spectroscopy, Raman spectroscopy, and confocal Raman imaging. Thus, human EPO (in vitro) and ex vivo activated eosinophils mediate biodegradation of SWCNTs: an observation that is relevant to pulmonary responses to these materials.

Uniform mesoporous silica coated iron oxide nanoparticles as a highly efficient, nontoxic MRI T(2) contrast agent with tunable proton relaxivities.

Monodisperse mesoporous silica (mSiO(2) ) coated superparamagnetic iron oxide (Fe(3) O(4) @mSiO(2) ) nanoparticles (NPs) have been developed as a potential magnetic resonance imaging (MRI) T(2) contrast agent. To evaluate the effect of surface coating on MRI contrast efficiency, we examined the proton relaxivities of Fe(3) O(4) @mSiO(2) NPs with different coating thicknesses. It was found that the mSiO(2) coating has a significant impact on the efficiency of Fe(3) O(4) NPs for MRI contrast enhancement. The efficiency increases with the thickness of mSiO(2) coating and is much higher than that of the commercial contrast agents. Nuclear magnetic resonance (NMR) relaxometry of Fe(3) O(4) @mSiO(2) further revealed that mSiO(2) coating is partially permeable to water molecules and therefore induces the decrease of longitudinal relaxivity, r(1) . Biocompatibility evaluation of various sized (ca. 35-95 nm) Fe(3) O(4) @mSiO(2) NPs was tested on OC-k3 cells and the result showed that these particles have no negative impact on cell viability. The enhanced MRI efficiency of Fe(3) O(4) @mSiO(2) highlights these core-shell particles as highly efficient T(2) contrast agents with high biocompatibility.

Characterization of superparamagnetic iron oxide nanoparticles and its application in protein purification.

The application of surface modified magnetic adsorbent particles in combination with magnetic separation techniques has received considerable awareness in recent years. There is a particular need in protein purification and analysis for specific, functional and generic methods of protein binding on solid supports. Nanoscale superparamagnetic iron oxide particles have been used to purify a natural coagulant protein extracted from Moringa oleifera seeds. Spectrophotometric analysis of the coagulant protein was performed using synthetic clay solution as substrate. Protein binding with carboxyl and silica surface modified superparamagnetic iron oxide nanoparticles (SPION) were compared with the known carboxyl methyl cellulose (CMC) beads of approximately 1 microm. SPION modified with carboxyl surface showed higher binding capacity towards the coagulant protein compared to the CMC beads. The high surface area to volume ratio of the carboxyl-coated SPION resulted in high binding capacity and rapid adsorption kinetics of the crude protein extract. The purification and molecular weight of coagulant protein is analyzed by SDS-PAGE. This approach utilizes the most efficient, feasible and economical method of coagulant protein purification and it can also be applicable to other proteins that possess similar properties.

Visualization and analysis of superparamagnetic iron oxide nanoparticles in the inner ear by light microscopy and energy filtered TEM.

Nanoparticles as potential carriers for local drug transfer are an alternative to systemic drug delivery into the inner ear. We report on the first in vitro tests of a new ferrogel consisting of superparamagnetic iron oxide nanoparticles (SPIONs) and a Pluronic(®) F127 (PF127) copolymer. Pluronic copolymers possess a unique viscosity-adjustable property that makes PF127 gels easy to handle compared to conventional cross-linked hydrogels. This ferrogel was successfully tested in cadaver human temporal bones as well as in organotypic explant cultures of mouse inner ears. SPIONs were identified by light microscopy and localized with different imaging modes in energy-filtered transmission electron microscopy. Our approach shows a promising possibility to use iron oxide nanoparticles, which are suitable for visualization and characterization at both the light- and electron-microscopic levels. FROM THE CLINICAL EDITOR: The authors report the first in vitro tests of a new ferrogel consisting of superparamagnetic iron oxide nanoparticles (SPIONs) and a Pluronic® F127 (PF127) copolymer for drug delivery in the inner ear, demonstrasting a promising possibility to use iron oxide nanoparticles, which are suitable for visualization and characterization at both the light- and electron-microscopic levels.

MRI manifestation of novel superparamagnetic iron oxide nanoparticles in the rat inner ear.

AIM: Superparamagnetic iron oxide nanoparticles hierarchically coated with oleic acid and Pluronic F127 copolymers (POA@SPION) have shown exceptional T2 contrast enhancement. The aim of the present work was to investigate the MRI manifestation of POA@SPION in the inner ear. MATERIALS & METHODS: A total of 26 male Wister rats were selected for testing POA@SPION administered through intracochlear, intratympanic and intravenous routes. MRI was performed with a 4.7 T MR scanner. RESULTS & CONCLUSION: POA@SPION can be introduced into the perilymph space, after which it becomes widely distributed and can demonstrate the integrity of the perilymph-endolymph barrier. Positive highlighting of the endolymph compartment against the darkened perilymph was visualized for the first time. POA@SPION passed through the middle-inner ear barriers in only small amounts, but stayed in the perilymph for 3 days. They did not traverse the blood-perilymph barrier or blood-endolymph barrier. The inner ear distribution of POA@SPION was confirmed by histology. POA@SPION is a promising T2 negative contrast agent.

Synthesis and magnetic properties of bulk transparent PMMA/Fe-oxide nanocomposites.

PMMA/Fe-oxide nanocomposites are fabricated by a chemical method. Monodispersed Fe-oxide nanoparticles are well dispersed in the PMMA matrix by in situ polymerization, resulting in a bulk transparent polymeric nanocomposite. The magnetic behavior of the PMMA/Fe-oxide nanocomposites is investigated. The transparent PMMA/Fe-oxide nanocomposite has potentially interesting magneto-optic applications without compromising the advantages of a lightweight, noncorrosive polymeric material with very high transparency even for bulk samples.

Tailored magnetic nanoparticles for direct and sensitive detection of biomolecules in biological samples.

We developed nanoparticles with tailored magnetic properties for direct and sensitive detection of biomolecules in biological samples in a single step. Thermally blocked nanoparticles obtained by thermal hydrolysis, functionalized with specific ligands, are mixed with sample solutions, and the variation of the magnetic relaxation due to surface binding is used to detect the presence of biomolecules. The binding significantly increases the hydrodynamic volume of nanoparticles, thus changing their Brownian relaxation frequency which is measured by a specifically developed AC susceptometer. The system was tested for the presence of Brucella antibodies, a dangerous pathogen causing brucellosis with severe effects both on humans and animals, in serum samples from infected cows and the surface of the nanoparticles was functionalized with lipopolysaccharides (LPS) from Brucella abortus. The hydrodynamic volume of LPS-functionalized particles increased by 25-35% as a result of the binding of the antibodies, measured by changes in the susceptibility in an alternating magnetic field. The method has shown high sensitivity, with detection limit of 0.05 microg x mL(-1) of antibody in the biological samples without any pretreatment. This magnetic-based assay is very sensitive, cost-efficient, and versatile, giving a direct indication whether the animal is infected or not, making it suitable for point-of-care applications. The functionalization of tailored magnetic nanoparticles can be modified to suit numerous homogeneous assays for a wide range of applications.