Synthesis and characterization ofα-Fe2O3nanoparticles showing potential applications for sensing quaternary ammonium vapor at room temperature.

P-type and n-type metal oxide semiconductors are widely used in the manufacture of gas sensing materials, due to their excellent electronic, electrical and electrocatalytic properties. Hematite (α-Fe2O3) compound has been reported as a promising material for sensing broad types of gases, due to its affordability, good stability and semiconducting properties. In the present work, the efficient and easy-to-implement sol-gel method has been used to synthesizeα-Fe2O3nanoparticles (NPs). The TGA-DSC characterizations of the precursor gel provided information about the phase transformation temperature and the mass percentage of the hematite NPs. X-ray diffraction, transmission electron microscopy and x-ray photoelectron spectroscopy data analyses indicated the formation of two iron oxide phases (hematite and magnetite) when the NPs are subjected to thermal treatment at 400 °C. Meanwhile, only the hematite phase was determined for thermal annealing above 500 °C up to 800 °C. Besides, the crystallite size shows an increasing trend with the thermal annealing and no defined morphology. A clear reduction of surface defects, associated with oxygen vacancies was also evidenced when the annealing temperature was increased, resulting in changes on the electrical properties of hematite NPs. Resistive gas-sensing tests were carried out using hematite NPs + glycerin paste, to detect quaternary ammonium compounds. Room-temperature high sensitivity values (Sr âˆ¼ 4) have been obtained during the detection of ∼1 mM quaternary ammonium compounds vapor. The dependence of the sensitivity on the particle size, the mass ratio of NPs with respect to the organic ligand, changes in the dielectric properties, and the electrical conduction mechanism of gas sensing was discussed.

PolishEM: image enhancement in FIB-SEM.

SUMMARY: We have developed a software tool to improve the image quality in focused ion beam-scanning electron microscopy (FIB-SEM) stacks: PolishEM. Based on a Gaussian blur model, it automatically estimates and compensates for the blur affecting each individual image. It also includes correction for artifacts commonly arising in FIB-SEM (e.g. curtaining). PolishEM has been optimized for an efficient processing of huge FIB-SEM stacks on standard computers. AVAILABILITY AND IMPLEMENTATION: PolishEM has been developed in C. GPL source code and binaries for Linux, OSX and Windows are available at http://www.cnb.csic.es/%7ejjfernandez/polishem. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Colloidal Stability and Concentration Effects on Nanoparticle Heat Delivery for Magnetic Fluid Hyperthermia.

The heat produced by magnetic nanoparticles, when they are submitted to a time-varying magnetic field, has been used in many auspicious biotechnological applications. In the search for better performance in terms of the specific power absorption (SPA) index, researchers have studied the influence of the chemical composition, size and dispersion, shape, and exchange stiffness in morphochemical structures. Monodisperse assemblies of magnetic nanoparticles have been produced using elaborate synthetic procedures, where the product is generally dispersed in organic solvents. However, the colloidal stability of these rough dispersions has not received much attention in these studies, hampering experimental determination of the SPA. To investigate the influence of colloidal stability on the heating response of ferrofluids, we produced bimagnetic core@shell NPs chemically composed of a ZnMn mixed ferrite core covered by a maghemite shell. Aqueous ferrofluids were prepared with these samples using the electric double layer (EDL) as a strategy to maintain colloidal stability. By starting from a proper sample, ultrastable concentrated ferrofluids were achieved by both tuning the ion/counterion ratio and controlling the water content. As the colloidal stability mainly depends on the ion configuration on the surface of the magnetic nanoparticles, different levels of nanoparticle clustering are achieved by changing the ionic force and pH of the medium. Thus, the samples were submitted to two procedures of EDL destabilization, which involved dilution with an alkaline solution and a neutral pH viscous medium. The SPA results of all prepared ferrofluid samples show a reduction of up to half the efficiency of the standard sample when the ferrofluids are in a neutral pH or concentrated regime. Such results are explained in terms of magnetic dipolar interactions. Our results point to the importance of ferrofluid colloidal stability in a more reliable experimental determination of the NP heat generation performance.

Adjusting the Néel relaxation time of Fe3O4/Zn x Co1-x Fe2O4 core/shell nanoparticles for optimal heat generation in magnetic hyperthermia.

In this work it is shown a precise way to optimize the heat generation in high viscosity magnetic colloids, by adjusting the Néel relaxation time in core/shell bimagnetic nanoparticles, for magnetic fluid hyperthermia (MFH) applications. To pursue this goal, Fe3O4/Zn x Co1-x Fe2O4 core/shell nanoparticles were synthesized with 8.5 nm mean core diameter, encapsulated in a shell of ∼1.1 nm of thickness, where the Zn atomic ratio (Zn/(Zn + Co) at%) changes from 33 to 68 at%. The magnetic measurements are consistent with a rigid interface coupling between the core and shell phases, where the effective magnetic anisotropy systematically decreases when the Zn concentration increases, without a significant change of the saturation magnetization. Experiments of MFH of 0.1 wt% of these particles dispersed in water, in Dulbecco modified Eagles minimal essential medium, and a high viscosity butter oil, result in a large specific loss power (SLP), up to 150 W g-1, when the experiments are performed at 571 kHz and 200 Oe. The SLP was optimized adjusting the shell composition, showing a maximum for intermediate Zn concentration. This study shows a way to maximize the heat generation in viscous media like cytosol, for those biomedical applications that require smaller particle sizes.

Piconewton Mechanical Forces Promote Neurite Growth.

Investigations over half a century have indicated that mechanical forces induce neurite growth, with neurites elongating at a rate of 0.1-0.3 µm h-1 pN-1 when mechanical force exceeds a threshold, with this being identified as 400-1000 pN for neurites of PC12 cells. In this article, we demonstrate that neurite elongation of PC12 cells proceeds at the same previously identified rate on application of mechanical tension of ∼1 pN, which is significantly lower than the force generated in vivo by axons and growth cones. This observation raises the possibility that mechanical tension may act as an endogenous signal used by neurons for promoting neurite elongation.

The orientation of the neuronal growth process can be directed via magnetic nanoparticles under an applied magnetic field.

There is a growing body of evidence indicating the importance of physical stimuli for neuronal growth and development. Specifically, results from published experimental studies indicate that forces, when carefully controlled, can modulate neuronal regeneration. Here, we validate a non-invasive approach for physical guidance of nerve regeneration based on the synergic use of magnetic nanoparticles (MNPs) and magnetic fields (Ms). The concept is that the application of a tensile force to a neuronal cell can stimulate neurite initiation or axon elongation in the desired direction, the MNPs being used to generate this tensile force under the effect of a static external magnetic field providing the required directional orientation. In a neuron-like cell line, we have confirmed that MNPs direct the neurite outgrowth preferentially along the direction imposed by an external magnetic field, by inducing a net angle displacement (about 30°) of neurite direction. From the clinical editor: This study validates that non-invasive approaches for physical guidance of nerve regeneration based on the synergic use of magnetic nanoparticles and magnetic fields are possible. The hypothesis was confirmed by observing preferential neurite outgrowth in a cell culture system along the direction imposed by an external magnetic field.

Magnetic nanoparticles as intraocular drug delivery system to target retinal pigmented epithelium (RPE).

One of the most challenging efforts in drug delivery is the targeting of the eye. The eye structure and barriers render this organ poorly permeable to drugs. Quite recently the entrance of nanoscience in ocular drug delivery has improved the penetration and half-life of drugs, especially in the anterior eye chamber, while targeting the posterior chamber is still an open issue. The retina and the retinal pigment epithelium/choroid tissues, located in the posterior eye chamber, are responsible for the majority of blindness both in childhood and adulthood. In the present study, we used magnetic nanoparticles (MNPs) as a nanotool for ocular drug delivery that is capable of specific localization in the retinal pigmented epithelium (RPE) layer. We demonstrate that, following intraocular injection in Xenopus embryos, MNPs localize specifically in RPE where they are retained for several days. The specificity of the localization did not depend on particle size and surface properties of the MNPs used in this work. Moreover, through similar experiments in zebrafish, we demonstrated that the targeting of RPE by the nanoparticles is not specific for the Xenopus species.

Disruption of the mitochondrial network in a mouse model of Huntington's disease visualized by in-tissue multiscale 3D electron microscopy.

Huntington's disease (HD) is an inherited neurodegenerative disorder caused by an expanded CAG repeat in the coding sequence of huntingtin protein. Initially, it predominantly affects medium-sized spiny neurons (MSSNs) of the corpus striatum. No effective treatment is still available, thus urging the identification of potential therapeutic targets. While evidence of mitochondrial structural alterations in HD exists, previous studies mainly employed 2D approaches and were performed outside the strictly native brain context. In this study, we adopted a novel multiscale approach to conduct a comprehensive 3D in situ structural analysis of mitochondrial disturbances in a mouse model of HD. We investigated MSSNs within brain tissue under optimal structural conditions utilizing state-of-the-art 3D imaging technologies, specifically FIB/SEM for the complete imaging of neuronal somas and Electron Tomography for detailed morphological examination, and image processing-based quantitative analysis. Our findings suggest a disruption of the mitochondrial network towards fragmentation in HD. The network of interlaced, slim and long mitochondria observed in healthy conditions transforms into isolated, swollen and short entities, with internal cristae disorganization, cavities and abnormally large matrix granules.

Genotoxicity and heating Performance of VxFe3-xO4 nanoparticles in Health applications.

The applications of magnetic nanoparticles (MNPs) as biocatalysts in different biomedical areas have been evolved very recently. One of the main challenges in this field is to design affective MNPs surfaces with catalytically active atomic centres, while producing minimal toxicological side effects on the hosting cell or tissues. MNPs of vanadium spinel ferrite (VFe2O4) are a promising material for mimicking the action of natural enzymes in degrading harmful substrates due to the presence of active V5+ centres. However, the toxicity of this material has not been yet studied in detail enough to grant biomedical safety. In this work, we have extensively measured the structural, compositional, and magnetic properties of a series of VxFe3-xO4 spinel ferrite MNPs to assess the surface composition and oxidation state of V atoms, and also performed systematic and extensive in vitro cytotoxicity and genotoxicity testing required to assess their safety in potential clinical applications. We could establish the presence of V5+ at the particle surface even in water-based colloidal samples at pH 7, as well as different amounts of V2+ and V3+ substitution at the A and B sites of the spinel structure. All samples showed large heating efficiency with Specific Loss Power values up to 400 W/g (H0 = 30 kA/m; f = 700 kHz). Samples analysed for safety in human hepatocellular carcinoma (HepG2) cell line with up to 24h of exposure showed that these MNPs did not induce major genomic abnormalities such as micronuclei, nuclear buds, or nucleoplasmic bridges (MNIs, NBUDs, and NPBs), nor did they cause DNA double-strand breaks (DSBs) or aneugenic effects-types of damage considered most harmful to cellular genetic material. The present study is an essential step towards the use of these type of nanomaterials in any biomedical or clinical application.

Cell death induced by AC magnetic fields and magnetic nanoparticles: current state and perspectives.

This review analyses the advances in the field of magnetically induced cell death using intracellular magnetic nanoparticles (MNPs). Emphasis has been given to in vitro research results, discussing the action of radiofrequency (RF) waves on biological systems as well as those results of thermally induced cell death in terms of MNP cell interactions. Our main goal has been to provide a unified depiction of many recent experiments and theoretical models relevant to the effect of applied electromagnetic fields on MNPs after cellular uptake and the cytotoxicity assessment of MNPs. We have addressed the effects of RF waves used for in vitro magnetic hyperthermia on eukaryotic cells regarding physical modifications of the cellular local environment and cell viability.

Observation of magnetic vortex configuration in non-stoichiometric Fe3O4 nanospheres.

Theoretical and micromagnetic simulation studies of magnetic nanospheres with vortex configurations suggest that such nanostructured materials have technological advantages over conventional nanosystems for applications based on high-power-rate absorption and subsequent emission. However, full experimental evidence of magnetic vortex configurations in spheres of submicrometer size is still lacking. Here, we report the microwave irradiation fabrication of Fe3O4 nanospheres and establish their magnetic vortex configuration based on experimental results, theoretical analysis, and micromagnetic simulations. Detailed magnetic and electrical measurements, together with Mössbauer spectroscopy data, provide evidence of a loss of stoichiometry in vortex nanospheres owing to the presence of a surface oxide layer, defects, and a higher concentration of cation vacancies. The results indicate that the magnetic vortex spin configuration can be established in bulk spherical magnetite materials. This study provides crucial information that can aid the synthesis of magnetic nanospheres with magnetically tailored properties; consequently, they may be promising candidates for future technological applications based on three-dimensional magnetic vortex structures.

Direct Polyphenol Attachment on the Surfaces of Magnetite Nanoparticles, Using Vitis vinifera, Vaccinium corymbosum, or Punica granatum.

This study presents an alternative approach to directly synthesizing magnetite nanoparticles (MNPs) in the presence of Vitis vinifera, Vaccinium corymbosum, and Punica granatum derived from natural sources (grapes, blueberries, and pomegranates, respectively). A modified co-precipitation method that combines phytochemical techniques was developed to produce semispherical MNPs that range in size from 7.7 to 8.8 nm and are coated with a ~1.5 nm thick layer of polyphenols. The observed structure, composition, and surface properties of the MNPs@polyphenols demonstrated the dual functionality of the phenolic groups as both reducing agents and capping molecules that are bonding with Fe ions on the surfaces of the MNPs via -OH groups. Magnetic force microscopy images revealed the uniaxial orientation of single magnetic domains (SMDs) associated with the inverse spinel structure of the magnetite (Fe3O4). The samples' inductive heating (H0 = 28.9 kA/m, f = 764 kHz), measured via the specific loss power (SLP) of the samples, yielded values of up to 187.2 W/g and showed the influence of the average particle size. A cell viability assessment was conducted via the MTT and NRu tests to estimate the metabolic and lysosomal activities of the MNPs@polyphenols in K562 (chronic myelogenous leukemia, ATCC) cells.

Magnetically triggered nanocomposite membranes: a versatile platform for triggered drug release.

Drug delivery devices based on nanocomposite membranes containing thermoresponsive nanogels and superparamagnetic nanoparticles have been demonstrated to provide reversible, on-off drug release upon application (and removal) of an oscillating magnetic field. We show that the dose of drug delivered across the membrane can be tuned by engineering the phase transition temperature of the nanogel, the loading density of nanogels in the membrane, and the membrane thickness, allowing for on-state delivery of model drugs over at least 2 orders of magnitude (0.1-10 µg/h). The zero-order kinetics of drug release across the membranes permit drug doses from a specific device to be tuned according to the duration of the magnetic field. Drugs over a broad range of molecular weights (500-40000 Da) can be delivered by the same membrane device. Membrane-to-membrane and cycle-to-cycle reproducibility is demonstrated, suggesting the general utility of these membranes for drug delivery.

A magnetically triggered composite membrane for on-demand drug delivery.

Nanocomposite membranes based on thermosensitive, poly(N-isopropylacrylamide)-based nanogels and magnetite nanoparticles have been designed to achieve "on-demand" drug delivery upon the application of an oscillating magnetic field. On-off release of sodium fluorescein over multiple magnetic cycles has been successfully demonstrated using prototype membrane-based devices. The total drug dose delivered was directly proportional to the duration of the "on" pulse. The membranes were noncytotoxic, were biocompatible, and retained their switchable flux properties after 45 days of subcutaneous implantation.

Enhanced Cellular Transduction of Nanoparticles Resistant to Rapidly Forming Plasma Protein Coronas.

Nanoparticles (NPs) are increasingly being developed as biomedical platforms for drug/nucleic acid delivery and imaging. However, in biological fluids, NPs interact with a wide range of proteins that form a coating known as protein corona. Coronae can critically influence self-interaction and binding of other molecules, which can affect toxicity, promote cell activation, and inhibit general or specific cellular uptake. Glycosaminoglycan (GAG)-binding enhanced transduction (GET) is developed to efficiently deliver a variety of cargoes intracellularly; employing GAG-binding peptides, which promote cell targeting, and cell penetrating peptides (CPPs) which enhance endocytotic cell internalization. Herein, it is demonstrated that GET peptide coatings can mediate sustained intracellular transduction of magnetic NPs (MNPs), even in the presence of serum or plasma. NP colloidal stability, physicochemical properties, toxicity and cellular uptake are investigated. Using label-free snapshot proteomics, time-resolved profiles of human plasma coronas formed on functionalized GET-MNPs demonstrate that coronae quickly form (<1 min), with their composition relatively stable but evolving. Importantly GET-MNPs present a subtly different corona composition to MNPs alone, consistent with GAG-binding activities. Understanding how NPs interact with biological systems and can retain enhanced intracellular transduction will facilitate novel drug delivery approaches for cell-type specific targeting of new nanomaterials.

Lipid-Iron Nanoparticle with a Cell Stress Release Mechanism Combined with a Local Alternating Magnetic Field Enables Site-Activated Drug Release.

Most available cancer chemotherapies are based on systemically administered small organic molecules, and only a tiny fraction of the drug reaches the disease site. The approach causes significant side effects and limits the outcome of the therapy. Targeted drug delivery provides an alternative to improve the situation. However, due to the poor release characteristics of the delivery systems, limitations remain. This report presents a new approach to address the challenges using two fundamentally different mechanisms to trigger the release from the liposomal carrier. We use an endogenous disease marker, an enzyme, combined with an externally applied magnetic field, to open the delivery system at the correct time only in the disease site. This site-activated release system is a novel two-switch nanomachine that can be regulated by a cell stress-induced enzyme at the cellular level and be remotely controlled using an applied magnetic field. We tested the concept using sphingomyelin-containing liposomes encapsulated with indocyanine green, fluorescent marker, or the anticancer drug cisplatin. We engineered the liposomes by adding paramagnetic beads to act as a receiver of outside magnetic energy. The developed multifunctional liposomes were characterized in vitro in leakage studies and cell internalization studies. The release system was further studied in vivo in imaging and therapy trials using a squamous cell carcinoma tumor in the mouse as a disease model. In vitro studies showed an increased release of loaded material when stress-related enzyme and magnetic field was applied to the carrier liposomes. The theranostic liposomes were found in tumors, and the improved therapeutic effect was shown in the survival studies.

Single-step chemical synthesis of ferrite hollow nanospheres.

We report a single-step chemical synthesis of iron oxide hollow nanospheres with 9.3 nm in diameter. The sample presents a narrow particle diameter distribution and chemical homogeneity. The hollow nature of the particles is confirmed by HRTEM and HAADF STEM analysis. Electron and x-ray diffraction show that the outer material component is constituted by 2 nm ferrite crystals. Mössbauer data provide further evidence for the formation of iron oxide with high structural disorder, magnetically ordered at 4.2 K and superparamagnetism at room temperature. An unusual magnetic behavior under an applied field is reported, which can be explained by the large fraction of atoms existing at both inner and outer surfaces.

The relevance of Brownian relaxation as power absorption mechanism in Magnetic Hyperthermia.

The Linear Response Theory (LRT) is a widely accepted framework to analyze the power absorption of magnetic nanoparticles for magnetic fluid hyperthermia. Its validity is restricted to low applied fields and/or to highly anisotropic magnetic nanoparticles. Here, we present a systematic experimental analysis and numerical calculations of the specific power absorption for highly anisotropic cobalt ferrite (CoFe2O4) magnetic nanoparticles with different average sizes and in different viscous media. The predominance of Brownian relaxation as the origin of the magnetic losses in these particles is established, and the changes of the Specific Power Absorption (SPA) with the viscosity of the carrier liquid are consistent with the LRT approximation. The impact of viscosity on SPA is relevant for the design of MNPs to heat the intracellular medium during in vitro and in vivo experiments. The combined numerical and experimental analyses presented here shed light on the underlying mechanisms that make highly anisotropic MNPs unsuitable for magnetic hyperthermia.

Magnetic Graphene Oxide Nanocarrier for Targeted Delivery of Cisplatin: A Perspective for Glioblastoma Treatment.

Selective vectorization of Cisplatin (CisPt) to Glioblastoma U87 cells was exploited by the fabrication of a hybrid nanocarrier composed of magnetic γ-Fe2O3 nanoparticles and nanographene oxide (NGO). The magnetic component, obtained by annealing magnetite Fe3O4 and characterized by XRD measurements, was combined with NGO sheets prepared via a modified Hummer's method. The morphological and thermogravimetric analysis proved the effective binding of γ-Fe2O3 nanoparticles onto NGO layers. The magnetization measured under magnetic fields up to 7 Tesla at room temperature revealed superparamagnetic-like behavior with a maximum value of MS = 15 emu/g and coercivity HC ≈ 0 Oe within experimental error. The nanohybrid was found to possess high affinity towards CisPt, and a rather slow fractional release profile of 80% after 250 h. Negligible toxicity was observed for empty nanoparticles, while the retainment of CisPt anticancer activity upon loading into the carrier was observed, together with the possibility to spatially control the drug delivery at a target site.

Controlling the dominant magnetic relaxation mechanisms for magnetic hyperthermia in bimagnetic core-shell nanoparticles.

We report a simple and effective way to control the heat generation of a magnetic colloid under alternate magnetic fields by changing the shell composition of bimagnetic core-shell Fe3O4/ZnxCo1-xFe2O4 nanoparticles. The core-shell structure constitutes a magnetically-coupled biphase system, with an effective anisotropy that can be tuned by the substitution of Co2+ by Zn2+ ions in the shell. Magnetic hyperthermia experiments of nanoparticles dispersed in hexane and butter oil showed that the magnetic relaxation is dominated by Brown relaxation mechanism in samples with higher anisotropy (i.e., larger concentration of Co within the shell) yielding high specific power absorption values in low viscosity media as hexane. Increasing the Zn concentration of the shell, diminishes the magnetic anisotropy, which results in a change to a Néel relaxation that dominates the process when the nanoparticles are dispersed in a high-viscosity medium. We demonstrate that tuning the Zn contents at the shell of these exchange-coupled core/shell nanoparticles provides a way to control the magnetic anisotropy without loss of saturation magnetization. This ability is an essential prerequisite for most biomedical applications, where high viscosities and capturing mechanisms are present.