Hydroxyapatite-Coated SPIONs and Their Influence on Cytokine Release.

Hydroxyapatite- or calcium phosphate-coated iron oxide nanoparticles have a high potential for use in many biomedical applications. In this study, a co-precipitation method for the synthesis of hydroxyapatite-coated nanoparticles (SPIONHAp), was used. The produced nanoparticles have been characterized by dynamic light scattering, X-ray diffraction, vibrating sample magnetometry, Fourier transform infrared spectrometry, atomic emission spectroscopy, scanning electron microscopy, transmission electron microscopy, selected area diffraction, and energy-dispersive X-ray spectroscopy. The results showed a successful synthesis of 190 nm sized particles and their stable coating, resulting in SPIONHAp. Potential cytotoxic effects of SPIONHAp on EL4, THP-1, and Jurkat cells were tested, showing only a minor effect on cell viability at the highest tested concentration (400 µg Fe/mL). The results further showed that hydroxyapatite-coated SPIONs can induce minor TNF-α and IL-6 release by murine macrophages at a concentration of 100 µg Fe/mL. To investigate if and how such particles interact with other substances that modulate the immune response, SPIONHAp-treated macrophages were incubated with LPS (lipopolysaccharides) and dexamethasone. We found that cytokine release in response to these potent pro- and anti-inflammatory agents was modulated in the presence of SPIONHAp. Knowledge of this behavior is important for the management of inflammatory processes following in vivo applications of this type of SPIONs.

Investigation of magnetically driven passage of magnetic nanoparticles through eye tissues for magnetic drug targeting.

This paper elucidates the feasibility of magnetic drug targeting to the eye by using magnetic nanoparticles (MNPs) to which pharmaceutical drugs can be linked. Numerical simulations revealed that a magnetic field gradient of 20 T m-1 seems to be promising for dragging magnetic multicore nanoparticles of about 50 nm into the eye. Thus, a targeting magnet system made of superconducting magnets with a magnetic field gradient at the eye of about 20 T m-1 was simulated. For the proof-of-concept tissue experiments presented here the required magnetic field gradient of 20 T m-1 was realized by a permanent magnet array. MNPs with an optimized multicore structure were selected for this application by evaluating their stability against agglomeration of MNPs with different coatings in water for injections, physiological sodium chloride solution and biological media such as artificial tear fluid. From these investigations, starch turned out to be the most promising coating material because of its stability in saline fluids due to its steric stabilization mechanism. To evaluate the passage of MNPs through the sclera and cornea of the eye tissues of domestic pigs (Sus scrofa domesticus), a three-dimensionally printed setup consisting of two chambers (reservoir and target chamber) separated by the eye tissue was developed. With the permanent magnet array emulating the magnetic field gradient of the superconducting setup, experiments on magnetically driven transport of the MNPs from the reservoir chamber into the target chamber via the tissue were performed. The resulting concentration of MNPs in the target chamber was determined by means of quantitative magnetic particle spectroscopy. It was found that none of the tested particles passed the cornea, but starch-coated particles could pass the sclera at a rate of about 5 ng mm-2 within 24 h. These results open the door for future magnetic drug targeting to the eye.

Synthesis and Characterization of Citrate-Stabilized Gold-Coated Superparamagnetic Iron Oxide Nanoparticles for Biomedical Applications.

Surface-functionalized gold-coated superparamagnetic iron oxide nanoparticles (Au-SPIONs) may be a useful tool in various biomedical applications. To obtain Au-SPIONs, gold salt was precipitated onto citrate-stabilized SPIONs (Cit-SPIONs) using a simple, aqueous one-pot technique inspired by the Turkevich method of gold nanoparticle synthesis. By the further stabilization of the Au-SPION surface with additional citrate (Cit-Au-SPIONs), controllable and reproducible Z-averages enhanced long-term dispersion stability and moderate dispersion pH values were achieved. The citrate concentration of the reaction solution and the gold/iron ratio was found to have a major influence on the particle characteristics. While the gold-coating reduced the saturation magnetization to 40.7% in comparison to pure Cit-SPIONs, the superparamagnetic behavior of Cit-Au-SPIONs was maintained. The formation of nanosized gold on the SPION surface was confirmed by X-ray diffraction measurements. Cit-Au-SPION concentrations of up to 100 µg Fe/mL for 48 h had no cytotoxic effect on Jurkat cells. At a particle concentration of 100 µg Fe/mL, Jurkat cells were found to take up Cit-Au-SPIONs after 24 h of incubation. A significantly higher attachment of thiol-containing L-cysteine to the particle surface was observed for Cit-Au-SPIONs (53%) in comparison to pure Cit-SPIONs (7%).

Protein corona formation and its constitutional changes on magnetic nanoparticles in serum featuring a polydehydroalanine coating: effects of charge and incubation conditions.

The inevitable formation of a protein corona upon contact of nanoparticles with different biological fluids is of great interest in the context of biomedical applications. It is well established that the surface chemistry of the respective nanomaterial has tremendous impact on protein adsorption, both in terms of the actual amount as well as the type of proteins adsorbed. In that regard, especially polyzwitterions are discussed as coating materials as they are known to partially inhibit protein adsorption. We herein present comparative incubation studies on iron oxide nanoparticles (either single core (SPION) or multicore nanoparticles (MCNP)) after coating with either polyanionic or polyzwitterionic polymeric shells based on polydehydroalanine (PDha). Apart from varying surface charge and chemistry, also the influence of incubation time and temperature on the formation and composition of a protein corona upon exposure to fetal calf serum was investigated. The amounts of adsorbed biomolecules were determined using thermogravimetric analysis. SDS-PAGE experiments revealed information on protein composition as major components of the biomolecule corona. Our results show that distinctly lower amounts of proteins are adsorbed onto polyzwitterionic hybrid nanoparticles in general, but also the corona composition varies as indicated by elevated relative ratios of medium molecular weight proteins (i.e. proteins 25-100 kDa) estimated by non-specific silver protein staining. In addition, increasing relative amounts of albumin (67 kDa) via specific Western blot assays on PDha-coated MCNP are detected.

Zwitterionic Iron Oxide (γ-Fe2 O3 ) Nanoparticles Based on P(2VP-grad-AA) Copolymers.

This study presents the synthesis and characterization of zwitterionic core-shell hybrid nanoparticles consisting of a core of iron oxide multicore nanoparticles (MCNPs, γ-Fe2 O3 ) and a shell of sultonated poly(2-vinylpyridine-grad-acrylic acid) copolymers. The gradient copolymers are prepared by reversible addition fragmentation chain transfer polymerization of 2-vinylpyridine (2VP), followed by the addition of tert-butyl acrylate and subsequent hydrolysis. Grafting of P(2VP-grad-AA) onto MCNP results in P(2VP-grad-AA)@MCNP, followed by quaternization using 1,3-propanesultone-leading to P(2VPS -grad-AA)@MCNP with a zwitterionic shell. The resulting particles are characterized by transmission electron microscopy, dynamic light scattering, and thermogravimetric analysis measurements, showing particle diameters of ≈70-90 nm and an overall content of the copolymer shell of ≈10%. Turbidity measurements indicate increased stability toward secondary aggregation after coating if compared to the pristine MCNP and additional cytotoxicity tests do not reveal any significant influence on cell viability.

Magnetic particle hyperthermia--a promising tumour therapy?

We present a critical review of the state of the art of magnetic particle hyperthermia (MPH) as a minimal invasive tumour therapy. Magnetic principles of heating mechanisms are discussed with respect to the optimum choice of nanoparticle properties. In particular, the relation between superparamagnetic and ferrimagnetic single domain nanoparticles is clarified in order to choose the appropriate particle size distribution and the role of particle mobility for the relaxation path is discussed. Knowledge of the effect of particle properties for achieving high specific heating power provides necessary guidelines for development of nanoparticles tailored for tumour therapy. Nanoscale heat transfer processes are discussed with respect to the achievable temperature increase in cancer cells. The need to realize a well-controlled temperature distribution in tumour tissue represents the most serious problem of MPH, at present. Visionary concepts of particle administration, in particular by means of antibody targeting, are far from clinical practice, yet. On the basis of current knowledge of treating cancer by thermal damaging, this article elucidates possibilities, prospects, and challenges for establishment of MPH as a standard medical procedure.

Delivery of TGFß3 from Magnetically Responsive Coaxial Fibers Reduces Spinal Cord Astrocyte Reactivity In Vitro.

A spinal cord injury (SCI) compresses the spinal cord, killing neurons and glia at the injury site and resulting in prolonged inflammation and scarring that prevents regeneration. Astrocytes, the main glia in the spinal cord, become reactive following SCI and contribute to adverse outcomes. The anti-inflammatory cytokine transforming growth factor beta 3 (TGFß3) has been shown to mitigate astrocyte reactivity; however, the effects of prolonged TGFß3 exposure on reactive astrocyte phenotype have not yet been explored. This study investigates whether magnetic core-shell electrospun fibers can be used to alter the release rate of TGFß3 using externally applied magnetic fields, with the eventual application of tailored drug delivery based on SCI severity. Magnetic core-shell fibers are fabricated by incorporating superparamagnetic iron oxide nanoparticles (SPIONs) into the shell and TGFß3 into the core solution for coaxial electrospinning. Magnetic field stimulation increased the release rate of TGFß3 from the fibers by 25% over 7 days and released TGFß3 reduced gene expression of key astrocyte reactivity markers by at least twofold. This is the first study to magnetically deliver bioactive proteins from magnetic fibers and to assess the effect of sustained release of TGFß3 on reactive astrocyte phenotype.

Magnetic Barium Hexaferrite Nanoparticles with Tunable Coercivity as Potential Magnetic Heating Agents.

Using magnetic nanoparticles (MNPs) for extracorporeal heating applications results in higher field strength and, therefore, particles of higher coercivity can be used, compared to intracorporeal applications. In this study, we report the synthesis and characterization of barium hexa-ferrite (BaFe12O19) nanoparticles as potential particles for magnetic heating. Using a precipitation method followed by high-temperature calcination, we first studied the influence of varied synthesis parameters on the particles' properties. Second, the iron-to-barium ratio (Fe/Ba = r) was varied between 2 and 12. Vibrating sample magnetometry, scanning electron microscopy and X-ray diffraction were used for characterization. A considerable influence of the calcination temperature (Tcal) was found on the resulting magnetic properties, with a decrease in coercivity (HC) from values above 370 kA/m for Tcal = 800-1000 °C to HC = 45-70 kA/m for Tcal = 1200 °C. We attribute this drop in HC mainly to the formation of entirely multi-domain particles at high Tcal. For the varying Fe/Ba ratios, increasing amounts of BaFe2O4 as an additional phase were detected by XRD in the small r (barium surplus) samples, lowering the particles' magnetization. A decrease in HC was found in the increased r samples. Crystal size ranged from 47 nm to 240 nm and large agglomerates were seen in SEM images. The reported particles, due to their controllable coercivity, can be a candidate for extracorporeal heating applications in the biomedical or biotechnological field.

Magnetic nanoparticle heating and heat transfer on a microscale: Basic principles, realities and physical limitations of hyperthermia for tumour therapy.

In this review article we present basic principles of magnetically induced heat generation of magnetic nanoparticles for application in magnetic particle hyperthermia. After explanation of heating mechanisms, the role of particle-particle as well as particle-tissue interactions is discussed with respect to achievable heating power of the particles inside the tumour. On the basis of heat transfer theory at the micro-scale, the balance between generated and dissipated heat inside the tumour and the resulting damaging effects for biological tissue is examined. The heating behaviour as a function of tumour size is examined in combination with feasible field strength and frequency. Numerical calculations and experimental investigations are used to show the lower tumour size limit for tumour heating to therapeutically suitable temperatures. In summary, this article illuminates practical aspects, limitations, and the state of the art for the application of magnetic heating in magnetic particle hyperthermia as thermal treatment of small tumours.

Effect of Europium Substitution on the Structural, Magnetic and Relaxivity Properties of Mn-Zn Ferrite Nanoparticles: A Dual-Mode MRI Contrast-Agent Candidate.

Magnetic nanoparticles (MNPs) have been widely applied as magnetic resonance imaging (MRI) contrast agents. MNPs offer significant contrast improvements in MRI through their tunable relaxivities, but to apply them as clinical contrast agents effectively, they should exhibit a high saturation magnetization, good colloidal stability and sufficient biocompatibility. In this work, we present a detailed description of the synthesis and the characterizations of europium-substituted Mn-Zn ferrite (Mn0.6Zn0.4EuxFe2-xO4, x = 0.00, 0.02, 0.04, 0.06, 0.08, 0.10, and 0.15, herein named MZF for x = 0.00 and EuMZF for others). MNPs were synthesized by the coprecipitation method and subsequent hydrothermal treatment, coated with citric acid (CA) or pluronic F127 (PF-127) and finally characterized by X-ray Diffraction (XRD), Inductively Coupled Plasma (ICP), Vibrating Sample Magnetometry (VSM), Fourier-Transform Infrared (FTIR), Dynamic Light Scattering (DLS) and MRI Relaxometry at 3T methods. The XRD studies revealed that all main diffraction peaks are matched with the spinel structure very well, so they are nearly single phase. Furthermore, XRD study showed that, although there are no significant changes in lattice constants, crystallite sizes are affected by europium substitution significantly. Room-temperature magnetometry showed that, in addition to coercivity, both saturation and remnant magnetizations decrease with increasing europium substitution and coating with pluronic F127. FTIR study confirmed the presence of citric acid and poloxamer (pluronic F127) coatings on the surface of the nanoparticles. Relaxometry measurements illustrated that, although the europium-free sample is an excellent negative contrast agent with a high r2 relaxivity, it does not show a positive contrast enhancement as the concentration of nanoparticles increases. By increasing the europium to x = 0.15, r1 relaxivity increased significantly. On the contrary, europium substitution decreased r2 relaxivity due to a reduction in saturation magnetization. The ratio of r2/r1 decreased from 152 for the europium-free sample to 11.2 for x = 0.15, which indicates that Mn0.6Zn0.4Eu0.15Fe1.85O4 is a suitable candidate for dual-mode MRI contrast agent potentially. The samples with citric acid coating had higher r1 and lower r2 relaxivities than those of pluronic F127-coated samples.

Optimization of Magnetic Cobalt Ferrite Nanoparticles for Magnetic Heating Applications in Biomedical Technology.

Using magnetic nanoparticles for extracorporeal magnetic heating applications in bio-medical technology allows higher external field amplitudes and thereby the utilization of particles with higher coercivities (HC). In this study, we report the synthesis and characterization of high coercivity cobalt ferrite nanoparticles following a wet co-precipitation method. Particles are characterized with magnetometry, X-ray diffraction, Mössbauer spectroscopy, transmission electron microscopy (TEM) and calorimetric measurements for the determination of their specific absorption rate (SAR). In the first series, CoxFe3-xO4 particles were synthesized with x = 1 and a structured variation of synthesis conditions, including those of the used atmosphere (O2 or N2). In the second series, particles with x = 0 to 1 were synthesized to study the influence of the cobalt fraction on the resulting magnetic and structural properties. Crystallite sizes of the resulting particles ranged between 10 and 18 nm, while maximum coercivities at room temperatures of 60 kA/m for synthesis with O2 and 37 kA/m for N2 were reached. Magnetization values at room temperature and 2 T (MRT,2T) up to 60 Am2/kg under N2 for x = 1 can be achieved. Synthesis parameters that lead to the formation of an additional phase when they exceed specific thresholds have been identified. Based on XRD findings, the direct correlation between high-field magnetization, the fraction of this antiferromagnetic byphase and the estimated transition temperature of this byphase, extracted from the Mössbauer spectroscopy series, we were able to attribute this contribution to akageneite. When varying the cobalt fraction x, a non-monotonous correlation of HC and x was found, with a linear increase of HC up to x = 0.8 and a decrease for x > 0.8, while magnetometry and in-field Mössbauer experiments demonstrated a moderate degree of spin canting for all x, yielding high magnetization. SAR values up to 480 W/g (@290 kHz, 69 mT) were measured for immobilized particles with x = 0.3, whit the external field amplitude being the limiting factor due to the high coercivities of our particles.

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.

Ferrimagnetic Large Single Domain Iron Oxide Nanoparticles for Hyperthermia Applications.

This paper describes the preparation and obtained magnetic properties of large single domain iron oxide nanoparticles. Such ferrimagnetic particles are particularly interesting for diagnostic and therapeutic applications in medicine or (bio)technology. The particles were prepared by a modified oxidation method of non-magnetic precursors following the green rust synthesis and characterized regarding their structural and magnetic properties. For increasing preparation temperatures (5 to 85 °C), an increasing particle size in the range of 30 to 60 nm is observed. Magnetic measurements confirm a single domain ferrimagnetic behavior with a mean saturation magnetization of ca. 90 Am2/kg and a size-dependent coercivity in the range of 6 to 15 kA/m. The samples show a specific absorption rate (SAR) of up to 600 W/g, which is promising for magnetic hyperthermia application. For particle preparation temperatures above 45 °C, a non-magnetic impurity phase occurs besides the magnetic iron oxides that results in a reduced net saturation magnetization.

Scavenging of bacteria or bacterial products by magnetic particles functionalized with a broad-spectrum pathogen recognition receptor motif offers diagnostic and therapeutic applications.

Sepsis is a dysregulated host response of severe bloodstream infections, and given its frequency of occurrence and high mortality rate, therapeutic improvements are imperative. A reliable biomimetic strategy for the targeting and separation of bacterial pathogens in bloodstream infections involves the use of the broad-spectrum binding motif of human GP-340, a pattern-recognition receptor of the scavenger receptor cysteine rich (SRCR) superfamily that is expressed on epithelial surfaces but not found in blood. Here we show that these peptides, when conjugated to superparamagnetic iron oxide nanoparticles (SPIONs), can separate various bacterial endotoxins and intact microbes (E. coli, S. aureus, P. aeruginosa and S. marcescens) with high efficiency, especially at low and thus clinically relevant concentrations. This is accompanied by a subsequent strong depletion in cytokine release (TNF, IL-6, IL-1ß, Il-10 and IFN-γ), which could have a direct therapeutic impact since escalating immune responses complicates severe bloodstream infections and sepsis courses. SPIONs are coated with aminoalkylsilane and capture peptides are orthogonally ligated to this surface. The particles behave fully cyto- and hemocompatible and do not interfere with host structures. Thus, this approach additionally aims to dramatically reduce diagnostic times for patients with suspected bloodstream infections and accelerate targeted antibiotic therapy. STATEMENT OF SIGNIFICANCE: Sepsis is often associated with excessive release of cytokines. This aspect and slow diagnostic procedures are the major therapeutic obstacles. The use of magnetic particles conjugated with small peptides derived from the binding motif of a broad-spectrum mucosal pathogen recognition protein GP-340 provides a highly efficient scavenging platform. These peptides are not found in blood and therefore are not subject to inhibitory mechanisms like in other concepts (mannose binding lectine, aptamers, antibodies). In this work, data are shown on the broad bacterial binding spectrum, highly efficient toxin depletion, which directly reduces the release of cytokines. Host cells are not affected and antibiotics not adsorbed. The particle bound microbes can be recultured without restriction and thus be used directly for diagnostics.

Magnetic multicore nanoparticles for hyperthermia--influence of particle immobilization in tumour tissue on magnetic properties.

When using magnetic nanoparticles as a heating source for magnetic particle hyperthermia it is of particular interest to know if the particles are free to move in the interstitial fluid or are fixed to the tumour tissue. The immobilization state determines the relaxation behaviour of the administered particles and thus their specific heating power. To investigate this behaviour, magnetic multicore nanoparticles were injected into experimentally grown tumours in mice and magnetic heating treatment was carried out in an alternating magnetic field (H = 25 kA m(-1), f = 400 kHz). The tested particles were well suited for magnetic heating treatment as they heated a tumour of about 100 mg by about 22 K within the first 60 s. Upon sacrifice, histological tumour examination showed that the particles form spots in the tissue with a mainly homogeneous particle distribution in these spots. The magnetic ex vivo characterization of the removed tumour tissue gave clear evidence for the immobilization of the particles in the tumour tissue because the particles in the tumour showed the same magnetic behaviour as immobilized particles. Therefore, the particles are not able to rotate and a temperature increase due to Brown relaxation can be neglected. To accurately estimate the heating potential of magnetic materials, the respective environments influencing the nanoparticle mobility status have to be taken into account.

Magnetic and fluorescent core-shell nanoparticles for ratiometric pH sensing.

This paper describes the preparation of nanoparticles composed of a magnetic core surrounded by two successive silica shells embedding two fluorophores, showing uniform nanoparticle size (50-60 nm in diameter) and shape, which allow ratiometric pH measurements in the pH range 5-8. Uncoated iron oxide magnetic nanoparticles (∼10 nm in diameter) were formed by the coprecipitation reaction of ferrous and ferric salts. Then, they were added to a water-in-oil microemulsion where the hydrophilic silica shells were obtained through hydrolysis and condensation of tetraethoxyorthosilicate together with the corresponding silylated dye derivatives-a sulforhodamine was embedded in the inner silica shell and used as the reference dye while a pH-sensitive fluorescein was incorporated in the outer shell as the pH indicator. The magnetic nanoparticles were characterized using vibrating sample magnetometry, dynamic light scattering, transmission electron microscopy, x-ray diffraction and Fourier transform infrared spectroscopy. The relationship between the analytical parameter, that is, the ratio of fluorescence between the sensing and reference dyes versus the pH was adjusted to a sigmoidal fit using a Boltzmann type equation giving an apparent pK(a) value of 6.8. The fluorescence intensity of the reference dye did not change significantly (∼3.0%) on modifying the pH of the nanoparticle dispersion. Finally, the proposed method was statistically validated against a reference procedure using samples of water and physiological buffer with 2% of horse serum, indicating that there are no significant statistical differences at a 95% confidence level.

Validity limits of the Néel relaxation model of magnetic nanoparticles for hyperthermia.

The derivation of the optimum mean diameter of magnetic nanoparticles (MNP) for hyperthermia as a tumour therapy in the literature is commonly reduced to application of the Néel relaxation model. Serious restrictions of this model for MNP for hyperthermia are discussed and a way is outlined to a more comprehensive model including hysteresis.

Biocompatible Magnetic Fluids of Co-Doped Iron Oxide Nanoparticles with Tunable Magnetic Properties.

Magnetite (Fe3O4) particles with a diameter around 10 nm have a very low coercivity (Hc) and relative remnant magnetization (Mr/Ms), which is unfavorable for magnetic fluid hyperthermia. In contrast, cobalt ferrite (CoFe2O4) particles of the same size have a very high Hc and Mr/Ms, which is magnetically too hard to obtain suitable specific heating power (SHP) in hyperthermia. For the optimization of the magnetic properties, the Fe2+ ions of magnetite were substituted by Co2+ step by step, which results in a Co doped iron oxide inverse spinel with an adjustable Fe2+ substitution degree in the full range of pure iron oxide up to pure cobalt ferrite. The obtained magnetic nanoparticles were characterized regarding their structural and magnetic properties as well as their cell toxicity. The pure iron oxide particles showed an average size of 8 nm, which increased up to 12 nm for the cobalt ferrite. For ferrofluids containing the prepared particles, only a limited dependence of Hc and Mr/Ms on the Co content in the particles was found, which confirms a stable dispersion of the particles within the ferrofluid. For dry particles, a strong correlation between the Co content and the resulting Hc and Mr/Ms was detected. For small substitution degrees, only a slight increase in Hc was found for the increasing Co content, whereas for a substitution of more than 10% of the Fe atoms by Co, a strong linear increase in Hc and Mr/Ms was obtained. Mössbauer spectroscopy revealed predominantly Fe3+ in all samples, while also verifying an ordered magnetic structure with a low to moderate surface spin canting. Relative spectral areas of Mössbauer subspectra indicated a mainly random distribution of Co2+ ions rather than the more pronounced octahedral site-preference of bulk CoFe2O4. Cell vitality studies confirmed no increased toxicity of the Co-doped iron oxide nanoparticles compared to the pure iron oxide ones. Magnetic heating performance was confirmed to be a function of coercivity as well. The here presented non-toxic magnetic nanoparticle system enables the tuning of the magnetic properties of the particles without a remarkable change in particles size. The found heating performance is suitable for magnetic hyperthermia application.

Magnetite-Arginine Nanoparticles as a Multifunctional Biomedical Tool.

Iron oxide nanoparticles are a promising platform for biomedical applications, both in terms of diagnostics and therapeutics. In addition, arginine-rich polypeptides are known to penetrate across cell membranes. Here, we thus introduce a system based on magnetite nanoparticles and the polypeptide poly-l-arginine (polyR-Fe3O4). We show that the hybrid nanoparticles exhibit a low cytotoxicity that is comparable to Resovist®, a commercially available drug. PolyR-Fe3O4 particles perform very well in diagnostic applications, such as magnetic particle imaging (1.7 and 1.35 higher signal respectively for the 3rd and 11th harmonic when compared to Resovist®), or as contrast agents for magnetic resonance imaging (R2/R1 ratio of 17 as compared to 11 at 0.94 T for Resovist®). Moreover, these novel particles can also be used for therapeutic purposes such as hyperthermia, achieving a specific heating power ratio of 208 W/g as compared to 83 W/g for Feridex®, another commercially available product. Therefore, we envision such materials to play a role in the future theranostic applications, where the arginine ability to deliver cargo into the cell can be coupled to the magnetite imaging properties and cancer fighting activity.