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The attractive electronic and magnetic properties together with their biocompatibility make iron-oxide nanoparticles appear as functional materials. In Fe-oxide nanoparticle (IONP) ensembles, it is crucial to enhance their performance thanks to controlled size, shape, and stoichiometry ensembles. In light of this, we conduct a comprehensive investigation in an ensemble of ca. 28 nm cuboid-shaped IONPs in which all the analyses concur with the coexistence of magnetite/maghemite phases in their cores. Here, we are disclosing the Verwey transition by temperature dependent (4–210 K) Raman spectroscopy., This work was supported by EU FP7 604448 (NanoMag) andMAT2017-83631-C3-R. Dr Norbert Schell is acknowledged forthe time at the HEMS beamline, and J. F. thanks MUDP (MST141-01415).

Background and objective: Nanoparticles present properties that can be applied to a wide range of fields such as biomedicine, electronics or optics. The type of properties depends on several characteristics, being some of them related with the particle structure. A proper characterization of nanoparticles is crucial since it could affect their applications. To characterize a particle shape and size, the nanotechnologists employ Electron Microscopy (EM) to obtain images of nanoparticles and perform measures over them. This task could be tedious, repetitive and slow, we present a Deep Learning method based on Convolutional Neural Networks (CNNs) to detect, segment, infer orientations and reconstruct microscope images of nanoparticles. Since machine learning algorithms depend on annotated data and there is a lack of annotated datasets of nanoparticles, our work makes use of artificial datasets of images resembling real nanoparticles photographs. Methods: Our work is divided into three tasks. Firstly, a method to create annotated datasets of artificial images resembling Scanning Electron Microscope (SEM). Secondly, two models of convolutional neural networks are trained using the artificial datasets previously generated, the first one is in charge of the detection and segmentation of the nanoparticles while the second one will infer the nanoparticle orientation. Finally, the 3D reconstruction module will recreate in a 3D scene the set of detected particles. Results: We have tested our method with five different shapes of basic nanoparticles: spheres, cubes, ellipsoids, hexagonal discs and octahedrons. An analysis of the reconstructions was conducted by manually comparing each of them with the real images. The results obtained have been promising, the particles are segmented and reconstructed accordingly to their shapes and orientations. Conclusions: We have developed a method for nanoparticle detection and segmentation in microscope images. Moreover, we can also infer a

Scientific interest in iron-oxides and in particular magnetite has been renewed due to the broad scope of their fascinating properties, which are finding applications in electronics and biomedicine. Specifically, iron oxide nanoparticles (IONPs) are gathering attraction in biomedicine. Their cores are usually constituted by a mixture of maghemite and magnetite phases. In view of this, to fine-tune the properties of an ensemble of IONPs towards their applications, it is essential to enhance mass fabrication processes towards the production of monodisperse IONPs with controlled size, shape, and stoichiometry. We exploit the vacancy sensitivity of the Verwey transition to detect the presence of magnetite. Here we provide direct evidence for the Verwey transition in an ensemble of IONPs through neutron diffraction. This transition is observed as a variation in the Fe magnetic moment at octahedral sites and, in turn, gives rise to a change of the net magnetic moment. Finally, we show this variation as the microscopic ingredient driving the characteristic kink that hallmarks the Verwey transition in thermal variation of magnetization.

The use of magnetic nanoparticles (MNPs) to locally increase the temperature at the nanoscale under the remote application of alternating magnetic fields (magnetic particle hyperthermia, MHT) has become an important subject of nanomedicine multidisciplinary research, focusing among other topics on the optimization of the heating performance of MNPs and their assemblies under the effect of the magnetic field. We report experimental data of heat released by MNPs using a wide range of anisometric shapes and their assemblies in different media. We outline a basic theoretical investigation, which assists the interpretation of the experimental data, including the effect of the size, shape and assembly of MNPs on the MNPs’ hysteresis loops and the maximum heat delivered. We report heat release data of anisometric MNPs, including nanodisks, spindles (elongated nanoparticles) and nanocubes, analysing, for a given shape, the size dependence. We study the MNPs either acting as individuals or assembled through a magnetic-field-assisted method. Thus, the physical geometrical arrangement of these anisometric particles, the magnetization switching and the heat release (by means of the determination of the specific adsorption rate, SAR values) under the application of AC fields have been analysed and compared in aqueous suspensions and after immobilization in agar matrix mimicking the tumour environment. The different nano-systems were analysed when dispersed at random or in assembled configurations. We report a systematic fall in the SAR for all anisometric MNPs randomly embedded in a viscous environment. However, certain anisometric shapes will have a less marked, an almost total preservation or even an increase in SAR when embedded in a viscous environment with certain orientation, in contrast to the measurements in water solution. Discrepancies between theoretical and experimental values reflect the complexity of the systems due to the interplay of different factors such as siz

Superparamagnetic iron oxide nanoparticles are one of the most prominent agents used in theranostic applications, with MRI imaging the main application assessed. The biomolecular interface formed on the surface of a nanoparticle in a biological medium determines its behaviour in vitro and in vivo. In this study, we have compared the formation of the protein corona on highly monodisperse iron oxide nanoparticles with two different coatings, dimercaptosuccinic acid (DMSA), and after conjugation, with a bifunctional polyethylene glycol (PEG)-derived molecule (2000 Da) in the presence of Wistar rat plasma. The protein fingerprints around the nanoparticles were analysed in an extensive proteomic study. The results presented in this work indicate that the composition of the protein corona is very difficult to predict. Proteins from different functional categories—cell components, lipoproteins, complement, coagulation, immunoglobulins, enzymes and transport proteins—were identified in all samples with very small variability. Although both types of nanoparticles have similar amounts of bonded proteins, very slight differences in the composition of the corona might explain the variation observed in the uptake and biotransformation of these nanoparticles in Caco-2 and RAW 264.7 cells. Cytotoxicity was also studied using a standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Controlling nanoparticles’ reactivity to the biological environment by deciding on its surface functionalization may suggest new routes in the control of the biodistribution, biodegradation and clearance of multifunctional nanomedicines

Magnetic nanoparticles (MNPs) constitute promising nanomedicine tools based on the possibility of obtaining different actuations (for example, heating or mechanical response) triggered by safe remote stimuli. Particularly, the possibility of performing different tasks using the same entity constitutes a main research target towards optimizing the treatment. But such a goal represents, in general, a very difficult step because the requisites for achieving efficient responses for separate actuations are often disparate – if not completely incompatible. An example of this is the response of MNPs to external AC fields, which could in principle be exploited for either magneto-mechanical actuation (MMA) at low frequencies (tens of Hz); or heat release at high frequency (0.1–1 MHz range) for magnetic fluid hyperthermia (MFH). The problem is that efficient MMA involves large torque, the required material parameters for which are detrimental to high heating, thus hindering the possibility of effective alternation between both responses. To overcome such apparent incompatibility, we propose a simple approach based on the use of anisotropic MNPs. The key idea is that the AC-frequency change must be concurrent with a field-amplitude variation able to promote – or impede – the reversal over the shape-determined anisotropy energy barrier. This way it is possible to switch the particle response between an efficient (magnetically dissipationless) rotation regime at low-f, for MMA, and a “frozen” (non-rotatable) high-energy-dissipation regime at high-f, for MFH. Furthermore, we show that such an alternation can also be achieved within the same high-f MFH regime. We use combined Brownian dynamics and micromagnetic simulations, based on real experimental samples, to show how such a field threshold can be tuned to working conditions with hexagonal-disk shape anisotropy

Magnetic nanoparticles are being developed as structural and functional materials for use in diverse areas, including biomedical applications.Here, we report the synthesis of maghemite (γ-Fe2O3) nanoparticles with distinct morphologies: single-core and multicore, including hollow spheres and nanoflowers, prepared by the polyol process. We have used sodium acetate to control the nucleation and assembly process to obtain the different particle morphologies. Moreover, from samples obtained at different time steps during the synthesis, we have elucidated the formation mechanism of the nanoflowers: the initial phases of the reaction present a lepidocrocite (γ-FeOOH) structure, which suffers a fast dehydroxylation, transforming to an intermediate “undescribed” phase, possibly a partly dehydroxylated lepidocrocite, which after some incubation time evolves to maghemite nanoflowers. Once the nanoflowers have been formed, a crystallization process takes place, where the γ-Fe2O3 crystallites within the nanoflowers grow in size (from∼11 to 23 nm), but the particle size of the flower remains essentially unchanged (∼60 nm). Samples with different morphologies were coated with citric acid and their heating capacity in an alternating magnetic field was evaluated. We observe that nanoflowers with large cores (23 nm, controlled by annealing) densely packed (tuned by low NaAc concentration) offer 5 times enhanced heating capacity compared to that of the nanoflowers with smaller core sizes (15 nm), 4 times enhanced heating effect compared to that of the hollow spheres, and 1.5 times enhanced heating effect compared to that of single-core nanoparticles (36 nm) used in this work.

In the present study, we applied a regularized inversion method to extract the particle size, magnetic moment and relaxation-time distribution of magnetic nanoparticles from small-angle x-ray scattering (SAXS), DC magnetization (DCM) and AC susceptibility (ACS) measurements. For the measurements the particles were colloidally dispersed in water. At first approximation the particles could be assumed to be spherically shaped and homogeneously magnetized single-domain particles. As model functions for the inversion, we used the particle form factor of a sphere (SAXS), the Langevin function (DCM) and the Debye model (ACS). The extracted distributions exhibited features/peaks that could be distinctly attributed to the individually dispersed and non-interacting nanoparticles. Further analysis of these peaks enabled, in combination with a prior characterization of the particle ensemble by electron microscopy and dynamic light scattering, a detailed structural and magnetic characterization of the particles. Additionally, all three extracted distributions featured peaks, which indicated deviations of the scattering (SAXS), magnetization (DCM) or relaxation (ACS) behavior from the one expected for individually dispersed, homogeneously magnetized nanoparticles. These deviations could be mainly attributed to partial agglomeration (SAXS, DCM, ACS), uncorrelated surface spins (DCM) and/or intra-well relaxation processes (ACS). The main advantage of the numerical inversion method is that no ad hoc assumptions regarding the line shape of the extracted distribution functions are required, which enabled the detection of these contributions. We highlighted this by comparing the results with the results obtained by standard model fits, where the functional form of the distributions was a priori assumed to be log-normal shaped.

Single-core iron-oxide nanoparticles with nominal core diameters of 14 nm and 19 nm were analyzed with a variety of non-magnetic and magnetic analysis techniques, including transmission electron microscopy (TEM), dynamic light scattering (DLS), static magnetization vs. magnetic field (M-H) measurements, ac susceptibility (ACS) and magnetorelaxometry (MRX). From the experimental data, distributions of core and hydrodynamic sizes are derived. Except for TEM where a number-weighted distribution is directly obtained, models have to be applied in order to determine size distributions from the measurand. It was found that the mean core diameters determined from TEM, M-H, ACS and MRX measurements agree well although they are based on different models (Langevin function, Brownian and Néel relaxation times). Especially for the sample with large cores, particle interaction effects come into play, causing agglomerates which were detected in DLS, ACS and MRX measurements. We observed that the number and size of agglomerates can be minimized by sufficiently strong diluting the suspension.

To successfully develop biomedical applications for magnetic nanoparticles, it is imperative that these nanoreagents maintain their magnetic properties in vivo and that their by-products are safely metabolized. When placed in biological milieu or internalized into cells, nanoparticle aggregation degree can increase which could affect magnetic properties and metabolization. To evaluate these aggregation effects, we synthesized citric acid-coated iron oxide nanoparticles whose magnetic susceptibility can be modified by aggregation in agar dilutions and dextran-layered counterparts that maintain their magnetic properties unchanged. Macrophage models were used for in vitro uptake and metabolization studies, as these cells control iron homeostasis in the organism. Electron microscopy and magnetic susceptibility studies revealed a cellular mechanism of nanoparticle degradation, in which a small fraction of the particles is rapidly degraded while the remaining ones maintain their size. Both nanoparticle types produced similar iron metabolic profiles but these profiles differed in each macrophage model. Thus, nanoparticles induced iron responses that depended on macrophage programming. In vivo studies showed that nanoparticles susceptible to changes in magnetic properties through aggregation effects had different behavior in lungs, liver and spleen. Liver ferritin levels increased in these animals showing that nanoparticles are degraded and their by-products incorporated into normal metabolic routes. These data show that nanoparticle iron metabolization depends on cell type and highlight the necessity to assess nanoparticle aggregation in complex biological systems to develop effective in vivo biomedical applications. Statement of Significance Magnetic iron oxide nanoparticles have great potential for biomedical applications. It is however imperative that these nanoreagents preserve their magnetic properties once inoculated, and that their degradation products can be elimin

We demonstrate that the precipitator concentration plays a crucial role in the structure adopted (single-core, nanoflowers or hollow spheres), and we varied the recrystallization time to obtain nanoflowers with different crystallinity.7 The up above mentioned ¿superferrimagnetic¿ state will be studied in hollow spheres and nanoflowers. Both multi-core structures investigated in this work have core sizes in the limit of superparamagnetic-ferrimagnetic regime (ranging from 11 to 27 nm). All samples regardless of their structures show ferrimagnetic behaviour at low temperature but samples with crystal sizes below 20 nm display superparamagnetic behaviour at RT (Figure 2 left). While the particle size in the nanoflowers is maintained unchanged, XRD analysis have revealed that an increase in crystal size can be obtained. The magnetic properties of the nanostructures reflect not only the core size, that justifies the nearly bulk saturation magnetisation values, but also the collective behaviour in the case of the flower-like particles leading to a susceptibility enhancement.

The assembly of magnetic cores into regular structures may notably influence the properties displayed by a magnetic colloid. Here, key synthesis parameters driving the self-assembly process capable of organizing colloidal magnetic cores into highly regular and reproducible multi-core nanoparticles are determined. In addition, a self-consistent picture that explains the collective magnetic properties exhibited by these complex assemblies is achieved through structural, colloidal, and magnetic means. For this purpose, different strategies to obtain flower-shaped iron oxide assemblies in the size range 25–100 nm are examined. The routes are based on the partial oxidation of Fe(OH)2, polyol-mediated synthesis or the reduction of iron acetylacetonate. The nanoparticles are functionalized either with dextran, citric acid, or alternatively embedded in polystyrene and their long-term stability is assessed. The core size is measured, calculated, and modeled using both structural and magnetic means, while the Debye model and multi-core extended model are used to study interparticle interactions. This is the first step toward standardized protocols of synthesis and characterization of flower-shaped nanoparticles.

A three-step aqueous approach to obtain large (>50 nm) magnetite single-core particles has been developed. The steps are a) synthesis of antiferromagnetic nanoparticles, b) particle coating and c) subsequent reduction of the core material to magnetite. By variation of precursor material and process conditions, the synthesis yielded rhombohedra, discs or needles below 200 nm. A combination of X-ray diffraction, 57Fe Mössbauer spectroscopy and infrared spectroscopy confirmed magnetite to be the dominant final core material. From transmission electron microscopy, we identified porous structures after the reduction. Magnetic characterization of the different magnetic nanopaticles revealed strikingly different magnetic behaviour depending on their shape, internal structure and reduction process. We conclude that each of these parameters have to be considered in further characterization of large magnetite nanoparticles.

The assembly of magnetic cores into regular structures may notably influence the properties displayed by a magnetic colloid. In this work, key synthesis parameters driving the self-assembly process capable of organizing colloidal magnetic cores into highly regular and reproducible multi-core nanoparticles are determined. In addition, a self-consistent picture that explains the collective magnetic properties exhibited by these complex assemblies is achieved through structural, colloidal, and magnetic means. For this purpose, different strategies to obtain flower-shaped iron oxide assemblies in the size range 25–100 nm are examined. The routes are based on the partial oxidation of Fe(OH)2, polyol-mediated synthesis or the reduction of iron acetylacetonate. The nanoparticles are functionalized either with dextran, citric acid, or alternatively embedded in polystyrene and their long-term stability is assessed. The core size is measured, calculated, and modeled using both structural and magnetic means while the Debye model and multi-core extended model are used to study interparticle interactions. This is the first step toward standardized protocols of synthesis and characterization of flower-shaped nanoparticles.

Magnetite nanoparticles have been prepared by oriented aggregation exploiting the action of calix[8]arene, an organic macrocycle capable of complexing Fe ions, during the synthesis. Control over the degree of aggregation enables tuning of the morphology of the product, which can vary from multicore aggregated nanoparticles to nano-octahedra, with a dramatic change in the magnetic properties. Octahedral magnetite nanoparticles display ferrimagnetic behavior, which is typical of magnetite above 40 nm in size. In contrast, multicore nanostructures exhibit a narrower hysteresis loop and remarkable heating capacity under an alternating magnetic field. With the aim of producing a material useful for biomedical applications, all samples were made to be dispersible in water and biocompatible by ligand exchange with 2,3-dimercaptosuccinic acid. Their morphology and magnetic properties were maintained after functionalization, as well as their good colloidal properties, which were characterized by dynamic light scattering.

Recent developments indicate that magnetic nanoparticles could help to improve clinical practice in the treatment of cancer, most probably in synergy with other conventional treatments [1]. There already exist methods to obtain magnetic nanoparticles with the appropriate properties to be used in diagnosis and therapy but these properties need to be optimized to avoid its alteration after intravenous injection, via interaction between the nanoparticles and the blood components, aggregation in lysosomes inside cells or accumulation in tissues [2]. In this work we will describe a number of proven synthesis routes for magnetic nanoparticles intended for their use in biomedical applications [3]. We will show the effect of different characteristics of the magnetic colloids, such as particle size and size distribution, colloidal properties of the aqueous suspensions, such as hydrodynamic size and surface modification, and magnetic properties on their MRI relaxivity and heating capacity. Finally, it will be shown that magnetic nanoparticles biodistribution following systemic administration and its transformation over time can be tracked by AC magnetic susceptibility measurements, which allow identifying and quantifying magnetic nanoparticles in tissues, differentiating them from other endogenous species such as the ferritin iron cores [4].