Francisco J. Lázaro

Reactivity in the removal of SO2 and NOx on Co/Mg/Al mixed oxides derived from hydrotalcites

Abstract Metal containing hydrotalcites, where metal oxides present redox properties and hydrotalcite shows a basic character, appear to be new important environmental catalysts for the removal of SO x and NO x . Redox and basic properties of a mixed Co/Mg/Al oxide derived from hydrotalcites are tuned in order to achieve the optimal catalytic behavior required. This sample has been characterized showing that cobalt is present in two forms, as isolated and well dispersed paramagnetic ions, and as very small Co-containing particles (in the nanometric range), with an internal antiferromagnetic ordering at low temperature. The redox properties of cobalt allow the reduction of NO with propane at high temperatures and in presence of oxygen. The reduced cobalt species are proposed as the active sites. Nevertheless, for the removal of SO 2 and contrary to the case of Cu/Mg/Al samples, the addition of an oxidant as cerium oxide on Co/Mg/Al is necessary in order to oxidize SO 2 to SO 3 . In this case, similar results than those obtained with previously reported catalyst, i.e. cerium or copper–cerium hydrotalcite, are obtained. These results indicate that this catalyst could be an adequate material for the simultaneous removal of SO 2 and NO x in a FCC unit.

Dimercaptosuccinic acid-coated magnetite nanoparticles for magnetically guided in vivo delivery of interferon gamma for cancer immunotherapy

As radio- and chemotherapy-based cancer treatments affect both tumors and healthy tissue, cancer immunotherapy attempts to specifically enhance the natural immune response to tumor cells. In mouse models of cancer, we tested uniform dimercaptosuccinic acid (DMSA)-coated monodisperse magnetic nanoparticles as a delivery system for the anti-tumorigenic cytokine IFN-γ. IFN-γ-adsorbed DMSA-coated magnetic nanoparticles were targeted to the tumor site by application of an external magnetic field. We analyzed nanoparticle biodistribution before and after IFN-γ conjugation, as well as the efficiency of nanoparticle accumulation in tumors, IFN-γ release in the area of interest, and the effects of both on tumor development. At the tumor site, we observed a high degree of nanoparticle accumulation and of cytokine delivery, which led to increased T cell and macrophage infiltration and promoted an anti-angiogenic effect. The combined action led to a notable reduction in tumor size. Our findings indicate that IFN-γ-adsorbed DMSA-coated magnetite nanoparticles can be used as an efficient in vivo drug delivery system for tumor immunotherapy.

Long term biotransformation and toxicity of dimercaptosuccinic acid-coated magnetic nanoparticles support their use in biomedical applications

Although iron oxide magnetic nanoparticles (MNP) have been proposed for numerous biomedical applications, little is known about their biotransformation and long-term toxicity in the body. Dimercaptosuccinic acid (DMSA)-coated magnetic nanoparticles have been proven efficient for in vivo drug delivery, but these results must nonetheless be sustained by comprehensive studies of long-term distribution, degradation and toxicity. We studied DMSA-coated magnetic nanoparticle effects in vitro on NCTC 1469 non-parenchymal hepatocytes, and analyzed their biodistribution and biotransformation in vivo in C57BL/6 mice. Our results indicate that DMSA-coated magnetic nanoparticles have little effect on cell viability, oxidative stress, cell cycle or apoptosis on NCTC 1469 cells in vitro. In vivo distribution and transformation were studied by alternating current magnetic susceptibility measurements, a technique that permits distinction of MNP from other iron species. Our results show that DMSA-coated MNP accumulate in spleen, liver and lung tissues for extended periods of time, in which nanoparticles undergo a process of conversion from superparamagnetic iron oxide nanoparticles to other non-superparamagnetic iron forms, with no significant signs of toxicity. This work provides the first evidence of DMSA-coated magnetite nanoparticle biotransformation in vivo.

Identification of nonferritin mitochondrial iron deposits in a mouse model of Friedreich ataxia.

There is no effective treatment for the cardiomyopathy of the most common autosomal recessive ataxia, Friedreich ataxia (FA). This disease is due to decreased expression of the mitochondrial protein, frataxin, which leads to alterations in mitochondrial iron (Fe) metabolism. The identification of potentially toxic mitochondrial Fe deposits in FA suggests Fe plays a role in its pathogenesis. Studies using the muscle creatine kinase (MCK) conditional frataxin knockout mouse that mirrors the disease have demonstrated frataxin deletion alters cardiac Fe metabolism. Indeed, there are pronounced changes in Fe trafficking away from the cytosol to the mitochondrion, leading to a cytosolic Fe deficiency. Considering Fe deficiency can induce apoptosis and cell death, we examined the effect of dietary Fe supplementation, which led to body Fe loading and limited the cardiac hypertrophy in MCK mutants. Furthermore, this study indicates a unique effect of heart and skeletal muscle-specific frataxin deletion on systemic Fe metabolism. Namely, frataxin deletion induces a signaling mechanism to increase systemic Fe levels and Fe loading in tissues where frataxin expression is intact (i.e., liver, kidney, and spleen). Examining the mutant heart, native size-exclusion chromatography, transmission electron microscopy, Mössbauer spectroscopy, and magnetic susceptibility measurements demonstrated that in the absence of frataxin, mitochondria contained biomineral Fe aggregates, which were distinctly different from isolated mammalian ferritin molecules. These mitochondrial aggregates of Fe, phosphorus, and sulfur, probably contribute to the oxidative stress and pathology observed in the absence of frataxin.

Ac magnetic susceptibility study of in vivo nanoparticle biodistribution

We analysed magnetic nanoparticle biodistribution, before and after cytokine conjugation, in a mouse model by ac susceptibility measurements of the corresponding resected tissues. Mice received repeated intravenous injections of nanoparticle suspension for two weeks and they were euthanized 1 h after the last injection. In general, only 10% of the total injected nanoparticles after multiple exposures were found in tissues. The rest of the particles may probably be metabolized or excreted by the organism. Our findings indicate that the adsorption of interferon to DMSA-coated magnetic nanoparticles changes their biodistribution, reducing the presence of nanoparticles in lungs and therefore their possible toxicity. The specific targeting of the particles to tumour tissues by the use of an external magnetic field has also been studied. Magnetic nanoparticles were observed by transmission electron microscopy in the targeted tissue and quantified by ac magnetic susceptibility.

The role of dipolar interaction in the quantitative determination of particulate magnetic carriers in biological tissues

The use of magnetic ac susceptibility measurements of biological tissues in the quantitative determination of their particulate magnetic carrier content has been investigated. In a first step, an ad hoc series of agar dilutions of the superparamagnetic contrast agent Endorem, used as an example of magnetic carrier, has been characterized to determine the influence of the dipolar interaction. With this result in hand, the quantitative determination of the content of a magnetic carrier in the ex vivo liver and spleen tissues of rats, to which the same compound was previously administered, has been accomplished. It is shown that, by careful interpretation of the temperature dependent out-of-phase susceptibility profiles in the cryogenic range, it is possible to discern between the magnetic contribution of the carrier and that of biomineral iron, being able to detect magnetic carrier iron concentrations of the order of 1 microg Fe g(-1) dry tissue. At the usual dosages in humans, necessarily small to avoid toxicity, the amount of magnetic carrier in terms of elemental iron is small compared to physiological iron. The choice of their most salient property, that is, the magnetic moment, therefore makes the quantification possible even in such a minority proportion. By analysing the magnetic dynamics, through a method that just considers the in-phase and the out-of phase components of the susceptibility at only one frequency, it has been possible to decouple the carrier concentration from eventual local aggregations, opening the possibility of investigating the degree of particle clustering at a larger observation scale compared with transmission electron microscopy, and independently of physiological iron.

Iron speciation study in Hfe knockout mice tissues: Magnetic and ultrastructural characterisation

Liver, spleen and heart tissues of DBA/2 Hfe knockout mice have been characterised by low temperature AC magnetic susceptibility measurements together with Transmission Electron Microscopy (TEM) and Selected Area Electron Diffraction in order to investigate the chemical iron speciation in a murine model of iron overload diseases. With emphasis on ferritin-like species, the temperature dependent in-phase and out-of-phase susceptibility profiles agree with the elemental analysis in that, in this model, iron accumulation takes place in the hepatic tissue while in the spleen and heart tissues no differences have been observed between knockout and wild type animals. The comparison of the magnetic properties between perfused and non-perfused liver tissues has made it possible to estimate the magnetic contribution of usually present blood remains. The TEM observations reveal that, besides the isolated ferritins and ferritin-containing lysosomes-siderosomes present in the hepatocytes, other iron deposits, of heterogeneous size, morphology and crystalline structure (haematite and/or goethite), are present in the cytoplasm, near the membrane, and in extracellular spaces.

Iron oxide particles in large pore zeolites

Abstract The magnetic properties of iron-containing ETS-10 zeolite and its calcined variety have been studied by magnetic measurements. The results are consistent with the presence of paramagnetic ions and superparamagnetic clusters. Calcination results in a shift of the blocking temperatures, although their frequency dependence cannot be ascribed to non-interacting clusters. The hypothesis of cluster-glass like behaviour is discussed.

Quantitative magnetic analysis reveals ferritin-like iron as the most predominant iron-containing species in the murine Hfe-haemochromatosis.

Quantitative analysis of the temperature dependent AC magnetic susceptibility of freeze-dried mouse tissues from an Hfe hereditary haemochromatosis disease model indicates that iron predominantly appears biomineralised, like in the ferritin cores, in the liver, the spleen and duodenum. The distribution of the amount of ferritin-like iron between genders and genotypes coincides with that of elemental iron and nonheme iron. Importantly, the so-called paramagnetic iron, a quantity also determined from the magnetic data and indicative of nonmineralised iron forms, appears only marginally increased when iron overload takes place.

Effect of Anesthesia on Magnetic Nanoparticle Biodistribution After Intravenous Injection

The role of anesthesia on magnetic nanoparticle biodistribution among different organs after intravenous injection has been studied in a murine model. Animals were anesthetized by inhalation with isoflurane (0.5% in oxygen) or by intraperitoneal injection with a mixture of ketamine and xylazine. Then, monodisperse dimercaptosuccinic acid coated magnetic nanoparticles (diameter of 9.2 nm 1.2 nm) were administered intravenously to the animals. Lung and liver tissues were collected after the particle administration and the amount of particles in each tissue was determined by alternating current magnetic susceptibility measurements. Whereas the amount of particles that reaches the liver seems not to be affected by the anesthesia used, the amount of particles that reaches the lungs for inhaled isoflurane is three times less than for the intraperitoneally injected anesthetic.