Synthesis of Manganese Zinc Ferrite Nanoparticles in Medical-Grade Silicone for MRI Applications.

The aim of this project is to fabricate hydrogen-rich silicone doped with magnetic nanoparticles for use as a temperature change indicator in magnetic resonance imaging-guided (MRIg) thermal ablations. To avoid clustering, the particles of mixed MnZn ferrite were synthesized directly in a medical-grade silicone polymer solution. The particles were characterized by transmission electron microscopy, powder X-ray diffraction, soft X-ray absorption spectroscopy, vibrating sample magnetometry, temperature-dependent nuclear magnetic resonance relaxometry (20 °C to 60 °C, at 3.0 T), and magnetic resonance imaging (at 3.0 T). Synthesized nanoparticles were the size of 4.4 nm ± 2.1 nm and exhibited superparamagnetic behavior. Bulk silicone material showed a good shape stability within the study's temperature range. Embedded nanoparticles did not influence spin-lattice relaxation, but they shorten the longer component of spin-spin nuclear relaxation times of silicone's protons. However, these protons exhibited an extremely high r2* relaxivity (above 1200 L s-1 mmol-1) due to the presence of particles, with a moderate decrease in the magnetization with temperature. With an increased temperature decrease of r2*, this ferro-silicone can be potentially used as a temperature indicator in high-temperature MRIg ablations (40 °C to 60 °C).

Aqueous Dispersion of Manganese-Zinc Ferrite Nanoparticles Protected by PEG as a T2 MRI Temperature Contrast Agent.

Mixed manganese-zinc ferrite nanoparticles coated with PEG were studied for their potential usefulness in MRI thermometry as temperature-sensitive contrast agents. Particles in the form of an 8.5 nm core coated with a 3.5 nm layer of PEG were fabricated using a newly developed, one-step method. The composition of Mn0.48Zn0.46Fe2.06O4 was found to have a strong thermal dependence of magnetization in the temperature range between 5 and 50 °C. Nanoparticles suspended in an agar gel mimicking animal tissue and showing non-significant impact on cell viability in the biological test were studied with NMR and MRI over the same temperature range. For the concentration of 0.017 mg/mL of Fe, the spin-spin relaxation time T2 increased from 3.1 to 8.3 ms, while longitudinal relaxation time T1 shows a moderate decrease from 149.0 to 125.1 ms. A temperature map of the phantom exposed to the radial temperature gradient obtained by heating it with an 808 nm laser was calculated from T2 weighted spin-echo differential MR images. Analysis of temperature maps yields thermal/spatial resolution of 3.2 °C at the distance of 2.9 mm. The experimental relaxation rate R2 data of water protons were compared with those obtained from calculations using a theoretical model incorporating the motion averaging regime.

Coacervate Thermoresponsive Polysaccharide Nanoparticles as Delivery System for Piroxicam.

Low water solubility frequently compromises the therapeutic efficacy of drugs and other biologically active molecules. Here, we report on coacervate polysaccharide nanoparticles (CPNs) that can transport and release a model hydrophobic drug, piroxicam, to the cells in response to changes in temperature. The proposed, temperature-responsive drug delivery system is based on ionic derivatives of natural polysaccharides-curdlan and hydroxypropyl cellulose. Curdlan was modified with trimethylammonium groups, while the anionic derivative of hydroxypropyl cellulose was obtained by the introduction of styrenesulfonate groups. Thermally responsive nanoparticles of spherical shape and average hydrodynamic diameter in the range of 250-300 nm were spontaneously formed in water from the obtained ionic polysaccharides as a result of the coacervation process. Their morphology was visualized using SEM and AFM. The size and the surface charge of the obtained objects could be tailored by adjusting the polycation/polyanion ratio. Piroxicam (PIX) was effectively entrapped inside the nanoparticles. The release profile of the drug from the CPNs-PIX was found to be temperature-dependent in the range relevant for biomedical applications.

Gradient of zinc content in core-shell zinc ferrite nanoparticles - precise study on composition and magnetic properties.

A broad spectrum of applications of magnetic nanoparticles leads to the need for the precise tuning of their magnetic properties. In this study, a series of magnetite and zinc-ferrite nanoparticles were successfully prepared by modified high-temperature synthesis in a controlled gas atmosphere. Nanoparticles with different zinc to iron ratios and pure Fe3O4 were obtained. The structure of the nanoparticles was studied by transmission electron microscopy and Mössbauer spectroscopy. These revealed the single domain character of the nanoparticles and the influence of the synthesis temperature and zinc to iron ratio on their shape and size. Chemical structure was characterized by inductively coupled plasma optical emission spectroscopy, energy dispersive X-ray spectroscopy and thermogravimetric analysis. X-ray photoelectron spectroscopy coupled with an argon gas cluster ion beam (Ar-GCIB) allowed the study of subsequent layers of the nanoparticles without altering their chemical structure. This revealed the presence of a carbon layer on all nanoparticles consisting of capping agents used in the synthesis and revealed the core-shell character of the zinc ferrite particles. In addition, different types of zinc infusions in the nanoparticle structure were observed when using different Zn/Fe ratios. Finally, magnetic studies performed by means of vibrating sample magnetometry proved the superparamagnetic behavior of all the samples.

Mammalian Oocyte Analysis by MALDI MSI with Wet-Interface Matrix Deposition Technique.

Oocytes are a special kind of biological material. Here, the individual variability of a single cell is important. It means that the opportunity to obtain information about the lipid content from the analysis of a single cell is significant. In our study, we present a method for lipid analysis based on the MALDI-based mass spectrometry imaging (MSI) approach. Our attention was paid to the sample preparation optimization with the aid of a wet-interface matrix deposition system (matrix spraying). Technical considerations of the sample preparation process, such as the number of matrix layers and the position of the spraying nozzle during the matrix deposition, are presented in the article. Additionally, we checked if changing the 2,5-dihydroxybenzoic acid (DHB) and 9-Aminoacridine (9AA) matrix concentration and their solvent composition may improve the analysis. Moreover, the comparison of paraformaldehyde-fixed versus nonfixed cell analysis was performed. We hope that our approach will be helpful for those working on lipid analyses in extraordinary material such as a single oocyte. Our study may also offer clues for anybody interested in single-cell analysis with the aid of MALDI mass spectrometry imaging and the wet-interface matrix deposition method.

Aerogels based on cationically modified chitosan and poly(vinyl alcohol) for efficient capturing of viruses.

In this study, we developed a new filtering bioaerogel based on linear polyvinyl alcohol (PVA) and the cationic derivative of chitosan (N-[(2-hydroxy-3-trimethylamine) propyl] chitosan chloride, HTCC) with a potential antiviral application. A strong intermolecular network architecture was formed thanks to the introduction of linear PVA chains, which can efficiently interpenetrate the glutaraldehyde(GA)-crosslinked HTCC chains. The morphology of the obtained structures was examined using scanning electron microscopy (SEM) and atomic force microscopy (AFM). The aerogels and modified polymers' elemental composition (including the chemical environment) was determined using X-ray photoelectron spectroscopy (XPS). New aerogels with more than twice as much developed micro- and mesopore space and BET-specific surface area were obtained concerning the starting sample chitosan aerogel crosslinked by glutaraldehyde (Chit/GA). The results obtained from the XPS analysis showed the presence of cationic 3-trimethylammonium groups on the surface of the aerogel, which can interact with viral capsid proteins. No cytotoxic effect of HTCC/GA/PVA aerogel was also observed on fibroblast cells of the NIH3T3 line. Furthermore, the HTCC/GA/PVA aerogel has been shown that efficiently traps mouse hepatitis virus (MHV) from suspension. The presented concept of aerogel filters for virus capture based on modified chitosan and polyvinyl alcohol has a high application potential.

One-Step Preparation of Highly Stable Copper-Zinc Ferrite Nanoparticles in Water Suitable for MRI Thermometry.

Superparamagnetic ferrite nanoparticles coated with a polymer layer are widely used for biomedical applications. The objective of this work is to design nanoparticles as a magnetic resonance imaging (MRI) temperature-sensitive contrast agent. Copper-zinc ferrite nanoparticles coated with a poly(ethylene glycol) (PEG) layer are synthesized using a one-step thermal decomposition method in a polymer matrix. The resulting nanoparticles are stable in water and biocompatible. Using Mössbauer spectroscopy and magnetometry, it was determined that the grown nanoparticles exhibit superparamagnetic properties. Embedding these particles into an agarose gel resulted in significant modification of water proton relaxation times T 1, T 2, and T 2* determined by nuclear magnetic resonance measurements. The results of the spin-echo T 2-weighted MR images of an aqueous phantom with embedded Cu0.08Zn0.54Fe2.38O4 nanoparticles in the presence of a strong temperature gradient show a strong correlation between the temperature and the image intensity. The presented results support the hypothesis that CuZn ferrite nanoparticles can be used as a contrast agent for MRI thermometry.

Tailoring cellular microenvironments using scaffolds based on magnetically-responsive polymer brushes.

A variety of polymeric scaffolds with the ability to control cell detachment has been created for cell culture using stimuli-responsive polymers. However, the widely studied and commonly used thermo-responsive polymeric substrates always affect the properties of the cultured cells due to the temperature stimulus. Here, we present a different stimuli-responsive approach based on poly(3-acrylamidopropyl)trimethylammonium chloride) (poly(APTAC)) brushes with homogeneously embedded superparamagnetic iron oxide nanoparticles (SPIONs). Neuroblastoma cell detachment was triggered by an external magnetic field, enabling a non-invasive process of controlled transfer into a new place without additional mechanical scratching and chemical/biochemical compound treatment. Hybrid scaffolds obtained in simultaneous surface-initiated atom transfer radical polymerization (SI-ATRP) were characterized by atomic force microscopy (AFM) working in the magnetic mode, secondary ion mass spectrometry (SIMS), and X-ray photoelectron spectroscopy (XPS) to confirm the magnetic properties and chemical structure. Moreover, neuroblastoma cells were cultured and characterized before and after exposure to a neodymium magnet. Controlled cell transfer triggered by a magnetic field is presented here as well.

Selective magnetometry of superparamagnetic iron oxide nanoparticles in liquids.

We show that the properties of superparamagnetic iron oxide nanoparticles suspended in liquids can be effectively studied using Magnetic Circular Dichroism in Resonant Inelastic X-ray Scattering. Analysis of the spectral shape and magnetic contrast produced by this experiment enables an assessment of the site distribution and magnetic state of metal ions in the spinel phase. The selective magnetization profile of particles as derived from the field dependence of dichroism empowers an estimation of particle size distribution. Furthermore, the new proposed methodology discriminates sizes that are below the detection limits of X-ray and light scattering probes and that are difficult to spot in TEM.

Biorefinery Approach for Aerogels.

According to the International Energy Agency, biorefinery is "the sustainable processing of biomass into a spectrum of marketable bio-based products (chemicals, materials) and bioenergy (fuels, power, heat)". In this review, we survey how the biorefinery approach can be applied to highly porous and nanostructured materials, namely aerogels. Historically, aerogels were first developed using inorganic matter. Subsequently, synthetic polymers were also employed. At the beginning of the 21st century, new aerogels were created based on biomass. Which sources of biomass can be used to make aerogels and how? This review answers these questions, paying special attention to bio-aerogels' environmental and biomedical applications. The article is a result of fruitful exchanges in the frame of the European project COST Action "CA 18125 AERoGELS: Advanced Engineering and Research of aeroGels for Environment and Life Sciences".

Nanohydrogels Based on Self-Assembly of Cationic Pullulan and Anionic Dextran Derivatives for Efficient Delivery of Piroxicam.

A cationic derivative of pullulan was obtained by grafting reaction and used together with dextran sulfate to form polysaccharide-based nanohydrogel cross-linked via electrostatic interactions between polyions. Due to the polycation-polyanion interactions nanohydrogel particles were formed instantly and spontaneously in water. The nanoparticles were colloidally stable and their size and surface charge could be controlled by the polycation/polyanion ratio. The morphology of the obtained particles was visualized by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and atomic force microscopy (AFM). The resulting structures were spherical, with hydrodynamic diameters in the range of 100-150 nm. The binding constant (Ka) of a model drug, piroxicam, to the cationic pullulan (C-PUL) was determined by spectrophotometric measurements. The value of Ka was calculated according to the Benesi-Hildebrand equation to be (3.6 ± 0.2) × 103 M-1. After binding to cationic pullulan, piroxicam was effectively entrapped inside the nanohydrogel particles and released in a controlled way. The obtained system was efficiently taken up by cells and was shown to be biocompatible.

Homogeneous Embedding of Magnetic Nanoparticles into Polymer Brushes during Simultaneous Surface-Initiated Polymerization.

Here we present a facile and efficient method of controlled embedding of inorganic nanoparticles into an ultra-thin (<15 nm) and flat (~1.0 nm) polymeric coating that prevents unwanted aggregation. Hybrid polymer brushes-based films were obtained by simultaneous incorporation of superparamagnetic iron oxide nanoparticles (SPIONs) with diameters of 8⁻10 nm into a polycationic macromolecular matrix during the surface initiated atom transfer radical polymerization (SI-ATRP) reaction in an ultrasonic reactor. The proposed structures characterized with homogeneous distribution of separated nanoparticles that maintain nanometric thickness and strong magnetic properties are a good alternative for commonly used layers of crosslinked nanoparticles aggregates or bulk structures. Obtained coatings were characterized using atomic force microscopy (AFM) working in the magnetic mode, secondary ion mass spectrometry (SIMS), and X-ray photoelectron spectroscopy (XPS).

Halloysite-alkaline phosphatase system-A potential bioactive component of scaffold for bone tissue engineering.

Alkaline phosphatase (ALP) was sucessfully incorporated into the halloysite (HAL) nanotubes, as confirmed by FTIR-ATR and XRD analyses. The loading efficiency (LE) of ALP was found to be 13.5%, while its encapsulation efficiency (EE) was estimated to be around 27%, as determined using the Bradford test. The influence of the immobilization in HAL on the enzyme activity was measured using standard ALP activity assay. Immobilized ALP effectively induced the bomineralization process, as showed by SEM, EDS, and XRD studies. As a result, calcium phosphate was produced in the form of hydroxyapatite cauliflower-like structures, with a slight content of calcium hydroxide. Interestingly, the encapsulation of ALP guest molecules in the HAL nanotubes considerably increased its thermal stability, most probably due to the heat sink effect. The activity of HAL-bound ALP was also found to be pH-independent in the wide range of pH values (3-10) due to the amphoteric nature of the aluminum oxide lining the HAL nanotube internal surface. Due to an increased resistance to the unfavorable conditions, which are often encountered during scaffold preparation or sterilization, ALP-HAL nanocomposite material may constitute an attractive bioactive component of the scaffolds for bone regeneration.

One-Step Synthesis of Long Term Stable Superparamagnetic Colloid of Zinc Ferrite Nanorods in Water.

Synthesis of spinel zinc ferrite ultrafine needle-like particles that exhibit exceptional stability in aqueous dispersion (without any surfactants) and superparamagnetic response is reported. Comprehensive structural and magnetic characterization of the particles is performed using X-ray and electron diffraction, small angle X-ray scattering, transmission electron microscopy, dynamic light scattering, vibrating sample magnetometry, Mössbauer spectroscopy and high-resolution X-ray spectroscopy. It reveals nearly stoichiometric ZnFe2O4 nanorods with mixed spinel structure and unimodal size distribution of mean length of 20 nm and diameter of 5 nm. Measurements performed in aqueous and dried form shows that particles' properties are significantly changed as a result of drying.

Analysis of toxicity and anticancer activity of micelles of sodium alginate-curcumin.

BACKGROUND: Curcumin is a natural polyphenol with anti-inflammatory, chemopreventive and anticancer activity. However, its high hydrophobicity and poor bioavailability limit its medical application. The development of nanocarriers for curcumin delivery is an attractive approach to overcome its low bioavailability and fast metabolism in the liver. We synthesized a blood compatible alginate-curcumin conjugate, AA-Cur, which formed colloidally stable micelles of approximately 200 nm and, as previously shown, exerted strong cytotoxicity against mouse cancer cell lines. Here we analyze in vivo toxicity and antitumor activity of AA-Cur in two different mouse tumor models. METHOD: Potential toxicity of intravenously injected AA-Cur was evaluated by: i) analyses of blood parameters (morphology and biochemistry), ii) histology, iii) DNA integrity (comet assay), and iv) cytokine profiling (flow cytometry). Antitumor activity of AA-Cur was evaluated by measuring the growth of subcutaneously inoculated colon MC38-CEA- or orthotopically injected breast 4T1 tumor cells in control mice vs mice treated with AA-Cur. RESULTS: Injections of four doses of AA-Cur did not reveal any toxicity of the conjugate, thus indicating the safety of its use. AA-Cur elicited moderate anti-tumor activity toward colon MC38-CEA or breast 4T1 carcinomas. CONCLUSION: The tested conjugate of alginate and curcumin, AA-Cur, is non-toxic and safe, but exhibits limited anticancer activity.

A Hybrid System for Magnetic Hyperthermia and Drug Delivery: SPION Functionalized by Curcumin Conjugate.

Cancer is among the leading causes of death worldwide, thus there is a constant demand for new solutions, which may increase the effectiveness of anti-cancer therapies. We have designed and successfully obtained a novel, bifunctional, hybrid system composed of colloidally stabilized superparamagnetic iron oxide nanoparticles (SPION) and curcumin containing water-soluble conjugate with potential application in anticancer hyperthermia and as nanocarriers of curcumin. The obtained nanoparticulate system was thoroughly studied in respect to the size, morphology, surface charge, magnetic properties as well as some biological functions. The results revealed that the obtained nanoparticles, ca. 50 nm in diameter, were the agglomerates of primary particles with the magnetic, iron oxide cores of ca. 13 nm, separated by a thin layer of the applied cationic derivative of chitosan. These agglomerates were further coated with a thin layer of the sodium alginate conjugate of curcumin and the presence of both polymers was confirmed using thermogravimetry. The system was also proven to be applicable in magnetic hyperthermia induced by the oscillating magnetic field. A high specific absorption rate (SAR) of 280 [W/g] was registered. The nanoparticles were shown to be effectively uptaken by model cells. They were found also to be nontoxic in the therapeutically relevant concentration in in vitro studies. The obtained results indicate the high application potential of the new hybrid system in combination of magnetic hyperthermia with delivery of curcumin active agent.

Biocompatible and fluorescent superparamagnetic iron oxide nanoparticles with superior magnetic properties coated with charged polysaccharide derivatives.

Syntheses and characterizations of biocompatible superparamagnetic iron oxide nanoparticles with embedded curcumin and coated with ultrathin layer of hyaluronic acid-curcumin (HA-Cur) conjugate have been reported. Zeta potential measurements confirmed effective coating of native iron oxide nanoparticles stabilized by cationic derivative of chitosan (SPION-CCh) with the synthesized HA-Cur conjugate. Both SPIONs with embedded curcumin and the ones coated with HA-Cur (SPION-CCh/HA-Cur) revealed desired magnetic characteristics while fluorescent properties were much better for the coated nanoparticles. SPION-CCh/HA-Cur nanoparticles were shown to be very promising candidates for T2 MRI contrast agents as they can easily penetrate cell membrane and their relaxivity is exceptionally high (ca. 470mM-1s-1). They may be also tracked using confocal fluorescence microscopy due to the presence of fluorescent curcumin in the coating. In vitro studies indicated that the obtained SPIONs-CCh/HA-Cur were non-toxic for EA.hy926 endothelial cells.