How size, shape and assembly of magnetic nanoparticles give rise to different hyperthermia scenarios.

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 size, shape and nanoparticle assembly due to magnetic interactions. We demonstrate that magnetic assembly holds great potential for producing materials with high functional and structural diversity, as we transform our nanoscale building blocks (anisometric MNPs) into a material displaying enhanced SAR properties.

Reproducibility and Scalability of Magnetic Nanoheater Synthesis.

The application of magnetic nanoparticles requires large amounts of materials of reproducible quality. This work explores the scaled-up synthesis of multi-core iron oxide nanoparticles through the use of thermal decomposition in organic media and kilograms of reagents. To this end, we check the effect of extending the high temperature step from minutes to hours. To address the intrinsic variability of the colloidal crystallization nucleation process, the experiments were repeated and analyzed statistically. Due to the simultaneity of the nuclei growth and agglomeration steps, the nanostructure of the samples produced was a combination of single- and multi-core nanoparticles. The main characteristics of the materials obtained, as well as the reaction yields, were analyzed and compared. As a general rule, yield, particle size, and reproducibility increase when the time at high temperature is prolonged. The samples obtained were ranked in terms of the reproducibility of different structural, colloidal, and magnetic features. The capability of the obtained materials to act as nanoheaters in magnetic hyperthermia was assessed, showing a strong dependence on the crystallite size (calculated by X-ray diffraction), reflecting the nanoparticle volume with a coherent magnetization reversal.

Superparamagnetic nanosorbent for water purification: Assessment of the adsorptive removal of lead and methyl orange from aqueous solutions.

The present study describes the preparation of 50.3 nm superparamagnetic nanosorbents with high surface area for the adsorptive removal of lead and methyl orange from water. This material is based on the surface modification of iron oxide superparamagnetic nanoparticles with a double-shell coating of mesoporous silica whose porosity was increased up to 570 m2/g by the addition of a porogenic material and its calcination. The adsorptive performance of the nanosorbent was evaluated as a function of several parameters (e.g. solution pH, pollutant initial concentration, and contact time), concluding that pHs around 5 are needed to avoid precipitation of Pb2+ as Pb(OH)2 and the equilibrium adsorption capacity is reached after 2 h in all cases. The experimental data on the adsorption capacity of lead and methyl orange onto the nanosorbent were fit to a pseudo-second order kinetic model and Langmuir isotherm model. The maximum adsorption capacity value increases from 35 up to 50 mg/gNS for lead removal with increasing nanosorbent surface area. Contrary, for methyl orange the maximum adsorption goes up to 240 mg/gNS, indicating a larger nanosorbent surface affinity for the organic matter that is able to diffuse through the silica pores as probed by the intraparticle diffusion model. In addition, we found an good reusability (100% recovering after 4 sorption/desorption cycles for methyl orange removal), which makes of this magnetic nanosorbent suitable for remediation technologies.

Flower-like Mn-Doped Magnetic Nanoparticles Functionalized with αvß3-Integrin-Ligand to Efficiently Induce Intracellular Heat after Alternating Magnetic Field Exposition, Triggering Glioma Cell Death.

Despite the potential of magnetic nanoparticles (NPs) to mediate intracellular hyperthermia when exposed to an alternating magnetic field (AMF), several studies indicate that the intracellular heating capacity of magnetic NPs depends on factors such as cytoplasm viscosity, nanoparticle aggregation within subcellular compartments, and dipolar interactions. In this work, we report the design and synthesis of monodispersed flowerlike superparamagnetic manganese iron oxide NPs with maximized SAR (specific absorption rate) and evaluate their efficacy as intracellular heaters in the human tumor-derived glioblastoma cell line U87MG. Three main strategies to tune the particle anisotropy of the core and the surface to reach the maximum heating efficiency were adopted: (1) varying the crystalline anisotropy by inserting a low amount of Mn2+ in the inverse spinel structure, (2) varying the NP shape to add an additional anisotropy source while keeping the superparamagnetic behavior, and (3) maximizing NP-cell affinity through conjugation with a biological targeting molecule to reach the NP concentration required to increase the temperature within the cell. We investigate possible effects produced by these improved NPs under the AMF (f = 96 kHz, H = 47 kA/m) exposure in the glioblastoma cell line U87MG by monitoring the expression of hsp70 gene and reactive oxygen species (ROS) production, as both effects have been described to be induced by increasing the intracellular temperature. The induced cell responses include cellular membrane permeabilization and rupture with concomitant high ROS appearance and hsp70 expression, followed by cell death. The responses were largely limited to cells that contained the NPs exposed to the AMF. Our results indicate that the developed strategies to optimize particle anisotropy in this work are a promising guidance to improve the heating efficiency of magnetic NPs in the human glioma cell line.

Seed predation increases from the Arctic to the Equator and from high to low elevations.

Species interactions have long been predicted to increase in intensity toward the tropics and low elevations because of gradients in climate, productivity, or biodiversity. Despite their importance for understanding global ecological and evolutionary processes, plant-animal interaction gradients are particularly difficult to test systematically across large geographic gradients, and evidence from smaller, disparate studies is inconclusive. By systematically measuring postdispersal seed predation using 6995 standardized seed depots along 18 mountains in the Pacific cordillera, we found that seed predation increases by 17% from the Arctic to the Equator and by 17% from 4000 meters above sea level to sea level. Clines in total predation, likely driven by invertebrates, were consistent across treeline ecotones and within continuous forest and were better explained by climate seasonality than by productivity, biodiversity, or latitude. These results suggest that species interactions play predictably greater ecological and evolutionary roles in tropical, lowland, and other less seasonal ecosystems.

Unravelling the mechanisms that determine the uptake and metabolism of magnetic single and multicore nanoparticles in a Xenopus laevis model.

Multicore superparamagnetic nanoparticles have been proposed as ideal tools for some biomedical applications because of their high magnetic moment per particle, high specific surface area and long term colloidal stability. Through controlled aggregation and packing of magnetic cores it is possible to obtain not only single-core but also multicore and hollow spheres with internal voids. In this work, we compare toxicological properties of single and multicore nanoparticles. Both types of particles showed moderate in vitro toxicity (MTT assay) tested in Hep G2 (human hepatocellular carcinoma) and Caco-2 (human colorectal adenocarcinoma) cells. The influence of surface chemistry in their biological behavior was also studied after functionalization with O,O'-bis(2-aminoethyl) PEG (2000 Da). For the first time, these nanoparticles were evaluated in a Xenopus laevis model studying their whole organism toxicity and their impact upon iron metabolism. The degree of activation of the metabolic pathway depends on the size and surface charge of the nanoparticles which determine their uptake. The results also highlight the potential of Xenopus laevis model bridging the gap between in vitro cell-based assays and rodent models for toxicity assessment to develop effective nanoparticles for biomedical applications.

The internal structure of magnetic nanoparticles determines the magnetic response.

This work aims to emphasize that the magnetic response of single-domain magnetic nanoparticles (NPs) is driven by the NPs' internal structure, and the NP size dependencies of magnetic properties are overestimated. The relationship between the degree of the NPs' crystallinity and magnetic response is unambiguously demonstrated in eight samples of uniform maghemite/magnetite NPs and corroborated with the results obtained for about 20 samples of spinel ferrite NPs with different degrees of crystallinity. The NP samples were prepared by the thermal decomposition of an organic iron precursor subjected to varying reaction conditions, yielding variations in the NP size, shape and relative crystallinity. We characterized the samples by using several complementary methods, such as powder X-ray diffraction (PXRD), transmission electron microscopy (TEM), high resolution TEM (HR-TEM) and Mössbauer spectroscopy (MS). We evaluated the NPs' relative crystallinity by comparing the NP sizes determined from TEM and PXRD and further inspecting the NPs' internal structure and relative crystallinity by using HR-TEM. The results of the structural characterization were put in the context of the NPs' magnetic response. In this work, the highest saturation magnetization (Ms) was measured for the smallest but well-crystalline NPs, while the larger NPs exhibiting worse crystallinity revealed a lower Ms. Our results clearly demonstrate that the NP crystallinity level that is mirrored in the internal spin order drives the specific magnetic response of the single-domain NPs.

Versatile theranostics agents designed by coating ferrite nanoparticles with biocompatible polymers.

Three biocompatible polymers, polyethylene glycol (PEG), dextran and chitosan, have been used in this work to control the colloidal stability of magnetic nanoparticles (14 ± 5 nm in diameter) and to vary the aggregation state in order to study their effect on relaxometric and heating properties. Two different coating strategies have been deeply developed; one based on the formation of an amide bond between citric acid coated nanoparticles (NPs) and amine groups present on the polymer surface and the other based on the NP encapsulation. Relaxometric properties revealed that proton relaxation rates strongly depend on the coating layer hydrophilicity and the aggregation state of the particles due to the presence of magnetic interactions. Thus, while PEG coating reduces particle aggregation by increasing inter-particle spacing leading to reduction of both T1 and T2 relaxation, dextran and chitosan lead to an increase mainly in T2 values due to the aggregation of particles in bigger clusters where they are in close contact. Dextran and chitosan coated NPs have also shown a remarkable heating effect during the application of an alternating magnetic field. They have proved to be potential candidates as theranostic agents for cancer diagnosis and treatment. Finally, cytotoxicity of PEG conjugated NPs, which seem to be ideal for intravenous administration because of their small hydrodynamic size, was investigated resulting in high cell viability even at 0.2 mg Fe ml(-1) after 24 h of incubation. This suspension can be used as drug/biomolecule carrier for in vivo applications.

Subsurface imaging of silicon nanowire circuits and iron oxide nanoparticles with sub-10 nm spatial resolution.

Non-destructive subsurface characterization of nanoscale structures and devices is of significant interest in nanolithography and nanomanufacturing. In those areas, the accurate location of the buried structures and their nanomechanical properties are relevant for optimization of the nanofabrication process and the functionality of the system. Here we demonstrate the capabilities of bimodal and trimodal force microscopy for imaging silicon nanowire devices buried under an ultrathin polymer film. We resolve the morphology and periodicities of silicon nanowire pairs. We report a spatial resolution in the sub-10 nm range for nanostructures buried under a 70 nm thick polymer film. By using numerical simulations we explain the role of the excited modes in the subsurface imaging process. Independent of the bimodal or trimodal atomic force microscopy approach, the fundamental mode is the most suitable for tracking the topography while the higher modes modulate the interaction of the tip with the buried nanostructures and provide subsurface contrast.

Biotransformation of magnetic nanoparticles as a function of coating in a rat model.

Long-term in vivo studies in murine models have shown that DMSA-coated nanoparticles accumulate in spleen, liver and lung tissues during extended periods of time (at least up to 3 months) without any significant signs of toxicity detected. During that time, nanoparticles undergo a process of biotransformation either by reducing the size or the particle aggregation or both. Using a rat model, we have evaluated the transformations of magnetic nanoparticles injected at low doses. Particles with two different coatings, dimercaptosuccinic acid (NP-DMSA) and polyethylene glycol (NP-PEG-(NH2)2) have been administered to animals, to evaluate the role of coating in the degradation of the particles. We have found that low doses of magnetic nanoparticles are quickly metabolized by the animals. In fact, using a nanoparticle dose four times lower than in previous experiments, NP-DMSA were not observed 24 h after the administration either in the liver or in the lungs. Interestingly, an increased amount of ferritin, the iron storage protein, was observed in liver tissues from rats that were treated with the low dose of NP-DMSA in comparison with the control ones, suggesting a rapid metabolization of the particles into ferritin iron. On the other side we have found that, NP-PEG-(NH2)2 are still detectable in several organs 24 h after their administration at low doses. Probably, due to the longer circulation times of the NP-PEG-(NH2)2, there is a delay in the arrival of the particles to the tissue and this is the reason why we are able to see the particles 24 h post-administration. PEG coating could also be protecting the nanoparticles from rapid degradation of the reticuloendothelial system. Knowledge on the biodistribution, circulation time and degradation processes is required to gain a better understanding of the safety evaluation of this kind of nanomaterial for biomedical applications.

Bismuth labeling for the CT assessment of local administration of magnetic nanoparticles.

Many therapeutic applications of magnetic nanoparticles involve the local administration of nanometric iron oxide based materials as seeds for magnetothermia or drug carriers. A simple and widespread way of controlling the process using x-ray computed tomography (CT) scanners is desirable. The combination of iron and bismuth in one entity will increase the atenuation of x-rays, offering such a possibility. In order to check this possibility core-shell nanocrystals of iron oxide@bismuth oxide have been synthesized by an aqueous route and stabilized in water by polyethylene glycol (PEG), and we have evaluated their ability to generate contrast by CT and magnetic resonance imaging (MRI) to measure the radiopacity and proton relaxivities using phantoms. High-resolution scanning transmission electron microscopy (STEM) revealed that the material consists of a highly crystalline 8 nm core of maghemite and a 1 nm shell of bismuth atoms either isolated or clustered on the nanocrystal's surface. The comparison of µCT and MRI images of mice acquired in the presence of the contrast shows that when local accumulations of the magnetic nanoparticles take place, CT images are more superior in the localization of the magnetic nanoparticles than MRI images, which results in magnetic field inhomogeneity artifacts.

Synthesis methods to prepare single- and multi-core iron oxide nanoparticles for biomedical applications.

We review current synthetic routes to magnetic iron oxide nanoparticles for biomedical applications. We classify the different approaches used depending on their ability to generate magnetic particles that are either single-core (containing only one magnetic core, i.e. a single domain nanocrystal) or multi-core (containing several magnetic cores, i.e. single domain nanocrystals). The synthesis of single-core magnetic nanoparticles requires the use of surfactants during the particle generation, and careful control of the particle coating to prevent aggregation. Special attention has to be paid to avoid the presence of any toxic reagents after the synthesis if biomedical applications are intended. Several approaches exist to obtain multi-core particles based on the coating of particle aggregates; nevertheless, the production of multi-core particles with good control of the number of magnetic cores per particle, and of the degree of polydispersity of the core sizes, is still a difficult task. The control of the structure of the particles is of great relevance for biomedical applications as it has a major influence on the magnetic properties of the materials.

Prospects for magnetic nanoparticles in systemic administration: synthesis and quantitative detection.

Methods for the quantitative determination of magnetic nanoparticles in biological matrices, in the frame of biomedical applications, are required to evaluate the particles biodistribution after systemic administration. AC magnetic susceptibility measurements are an alternative method to quantify magnetic nanoparticles in tissues, being able to provide also information on the particle transformations over time and allowing the distinction of the particles from other endogenous species such as the ferritin iron cores. The protocol for particle quantification using AC magnetic susceptibility measurements is described in detail in this article. A summary of synthesis routes towards magnetic nanoparticles is also provided.

Biodistribution and pharmacokinetics of uniform magnetite nanoparticles chemically modified with polyethylene glycol.

The influence of polyethylene glycol (PEG) grafting on the pharmacokinetics, biodistribution and elimination of iron oxide nanoparticles is studied in this work. Magnetite nanoparticles (12 nm) were obtained via thermal decomposition of an iron coordination complex as a precursor. Particles were coated with meso-2,3-dimercaptosuccinic acid (DMSA) and conjugated to PEG-derived molecules by 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide (EDC) chemistry. Using a rat model, we explored the nanoparticle biodistribution pattern in blood and in different organs (liver, spleen and lungs) after intravenous administration of the product. The time of residence in blood was measured from the evolution of water proton relaxivities with time and Fe analysis in blood samples. The results showed that the residence time was doubled for PEG coated nanoparticles and consequently particle accumulation in liver and spleen was reduced. Post-mortem histological analyses showed no alterations in the liver and confirm heterogeneous distribution of NPs in the organ, in agreement with magnetic measurements and iron analysis. Finally, by successive magnetic resonance images we studied the evolution of contrast in the liver and measured the absorption, time of residence and excretion of nanoparticles in the liver during a one month period. On the basis of these results we propose different metabolic routes that determine the fate of magnetic nanoparticles.

Short-chain PEG molecules strongly bound to magnetic nanoparticle for MRI long circulating agents.

This study developed an approach for the synthesis of magnetic nanoparticles coated with three different polyethylene glycol (PEG)-derived molecules. The influence of the coating on different properties of the nanoparticles was studied. Magnetite nanoparticles (7 and 12 nm in diameter) were obtained via thermal decomposition of a coordination complex as an iron precursor to ensure nanoparticle homogeneity in size and shape. Particles were first coated with meso-2,3-dimercaptosuccinic acid by a ligand exchange process to remove oleic acid, followed by modification with three distinct short-chain PEG polymers, which were covalently bound to the nanoparticle surface via 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride activation of the carboxylic acids. In all cases, colloidal suspensions had hydrodynamic sizes <100 nm and low surface charge, demonstrating the effect of PEG coating on the aggregation properties and steric stabilization of the magnetic nanoparticles. The internalization and biocompatibility of these materials in the HeLa human cervical carcinoma cell line were tested. Cells preincubated with PEG-coated iron nanoparticles were visualized outside the cells, and their biocompatibility at high Fe concentrations was demonstrated using a standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Finally, relaxivity parameters (r1 and r2) were used to evaluate the efficiency of suspensions as magnetic resonance imaging contrast agents; the r2 value was similar to that for Resovist and up to four times higher than that for Sinerem, probably due to the larger nanoparticle size. The time of residence in blood of the nanoparticles measured from the relaxivity values, and the Fe content in blood was doubled for rats and rabbits due to the PEG on the nanoparticle surface. The results suggest that this PEGylation strategy for large magnetic nanoparticles (>10nm) holds promise for biomedical applications.

Synthesis and characterization of CoFe2O4 ferrite nanoparticles obtained by an electrochemical method.

Uniform size cobalt ferrite nanoparticles have been synthesized in one step using an electrochemical technique. Synthesis parameters such as the current density, temperature and stirring were optimized to produce pure cobalt ferrite. The nanoparticles have been investigated by means of magnetic measurements, Mössbauer spectroscopy, x-ray powder diffraction and transmission electron microscopy. The average size of the electrosynthesized samples was controlled by the synthesis parameters and this showed a rather narrow size distribution. The x-ray analysis shows that the CoFe(2)O(4) obtained presents a totally inverse spinel structure. The magnetic properties of the stoichiometric nanoparticles show ferromagnetic behavior at room temperature with a coercivity up to 6386 Oe and a saturation magnetization of 85 emu g(-1).

Investigation of a Mesoporous Silicon Based Ferromagnetic Nanocomposite.

A semiconductor/metal nanocomposite is composed of a porosified silicon wafer and embedded ferromagnetic nanostructures. The obtained hybrid system possesses the electronic properties of silicon together with the magnetic properties of the incorporated ferromagnetic metal. On the one hand, a transition metal is electrochemically deposited from a metal salt solution into the nanostructured silicon skeleton, on the other hand magnetic particles of a few nanometres in size, fabricated in solution, are incorporated by immersion. The electrochemically deposited nanostructures can be tuned in size, shape and their spatial distribution by the process parameters, and thus specimens with desired ferromagnetic properties can be fabricated. Using magnetite nanoparticles for infiltration into porous silicon is of interest not only because of the magnetic properties of the composite material due to the possible modification of the ferromagnetic/superparamagnetic transition but also because of the biocompatibility of the system caused by the low toxicity of both materials. Thus, it is a promising candidate for biomedical applications as drug delivery or biomedical targeting.

Functionalisation of glass with iron oxide nanoparticles produced by laser pyrolysis.

In the present work, a new process for depositing nanoparticle layers onto glass has been developed by using one of the most interesting nanoparticle generation technologies at the moment, which is based on the pyrolysis induced by laser of vapours combined with CVD of the particles onto glass. Nanoparticles prepared by this method were deposited into a hot silica substrate obtaining new nanocomposites with unique properties. The coated glasses present new specific functionalities such as colour, and interesting magnetic and optical properties. Control of the thickness and the iron oxide phase, either magnetic or not, has been achieved by adjusting the experimental conditions. Thus, thickness is controlled by the glass and the precursor temperature, while the iron phase is controlled by the precursor temperature and the nature and the flow of the carrier gas. This process is inexpensive, adaptable to current glass production technologies and takes place at atmospheric pressure.

[Assessment of the nutritional value of the menus served in school canteens on the island of Tenerife, Spain]. / Valoración nutricional de los menús escolares de los colegios públicos de la isla de Tenerife.

OBJECTIVE: To study the nutritional characteristics of the menus provided in the state primary schools of Tenerife and to assess whether they are adequate for the different age groups of school children. SCOPE AND METHODS: The study is conducted in 52 school canteens, with a population of 8,411 diners aged between 4 and 12 years old. 27 of the 52 school dinner services were managed directly and 25 were contracted out to catering companies. They were selected through a random sampling that was stratified by the different geographic areas of the island. A full menu was taken from each of them: first course, second course and dessert (in some cases, a dairy product, normally a piece of fruit). The food was recorded by weight. For assessing the nutritional input in the directly managed dining rooms, we took information on the menu, how it was prepared, the ingredients used and the proportion of each of these in each dish, the amount of oil and salt added, etc. Hence we calculate the proportion of each ingredient. We then weigh the different rations offered to the school children. In the case of the menus offered by catering companies, the quantity of the ration is weighed in the school dining room and, as the catering company supplies us with the breakdown of all the ingredients used in the dishes, we can determine the composition of the menus. To convert the food into nutrients, we used the Dietsource V 1.0 programme. The school menu is broken down using the diet, dish and food management plan, to give the proportions of active ingredients used, and the Recommended Inputs for the Spanish population are used as a reference for evaluating the nutritional quality of the diet, taking the average of the recommended value for the different age groups for each of the parameters. RESULTS: The carbohydrates account for 54% of the total energy, lipids 27% and proteins 19%. The mean content and standard error for cholesterol is 77.53 +/- 64.30 mg, so the mean cholesterol input per 1,000 kcal is 109 mg/1,000 kcal. Saturated fatty acids contribute 8.6% of the calorie input, monounsaturated fatty acids 11.7% and polyunsaturated fatty acids 9.7%. The fibre input per 1,000 kcal is 11 g. CONCLUSIONS: The energy value of the school menu is adequate, the percentage content of proteins is slightly high and the lipid and carbohydrate contents are within the limits. The percentage content of fatty acids is adequate, as are the percentage contents of cholesterol and fibre. The vitamin and mineral contents are appropriate, with the exception of iodine, zinc, iron and vitamins D, E and riboflavin, where there is a deficit, especially for the older children.