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Addition of Co2(Co)9 and Ru3(CO)12 on preformed monodisperse iron(0) nanoparticles (Fe(0) NPs) at 150 °C under H2 leads to monodisperse core-shell Fe@FeCo NPs and to a thin discontinuous Ru(0) layer supported on the initial Fe(0) NPs. The new complex NPs were studied by state-of-the-art transmission electron microscopy techniques as well as X-ray diffraction, Mössbauer spectroscopy, and magnetic measurements. These particles display large heating powers (SAR) when placed in an alternating magnetic field. The combination of magnetic and surface catalytic properties of these novel objects were used to demonstrate a new concept: the possibility of performing Fischer-Tropsch syntheses by heating the catalytic nanoparticles with an external alternating magnetic field.

RESUMEN

Combining high-frequency alternating magnetic fields (AMF) and magnetic nanoparticles (MNPs) is an efficient way to induce biological responses through several approaches: magnetic hyperthermia, drug release, controls of gene expression and neurons, or activation of chemical reactions. So far, these experiments cannot be analyzed in real-time during the AMF application. A miniaturized electromagnet fitting under a confocal microscope is built, which produces an AMF of frequency and amplitude similar to the ones used in magnetic hyperthermia. AMF application induces massive damages to tumoral cells having incorporated nanoparticles into their lysosomes without affecting the others. Using this setup, real-time analyses of molecular events occurring during AMF application are performed. Lysosome membrane permeabilization and reactive oxygen species production are detected after only 30 min of AMF application, demonstrating they occur at an early stage in the cascade of events leading eventually to cell death. Additionally, lysosomes self-assembling into needle-shaped organization under the influence of AMF is observed in real-time. This experimental approach will permit to get a deeper insight into the physical, molecular, and biological process occurring in several innovative techniques used in nanomedecine based on the combined use of MNPs and high-frequency magnetic fields.

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RESUMEN

Nanotherapy using targeted magnetic nanoparticles grafted with peptidic ligands of receptors overexpressed in cancers is a promising therapeutic strategy. However, nanoconjugation of peptides can dramatically affect their properties with respect to receptor recognition, mechanism of internalization, intracellular trafficking, and fate. Furthermore, investigations are needed to better understand the mechanism whereby application of an alternating magnetic field to cells containing targeted nanoparticles induces cell death. Here, we designed a nanoplatform (termed MG-IONP-DY647) composed of an iron oxide nanocrystal decorated with a ligand of a G-protein coupled receptor, the cholecystokinin-2 receptor (CCK2R) that is overexpressed in several malignant cancers. MG-IONP-DY647 did not stimulate inflammasome of Raw 264.7 macrophages. They recognized cells expressing CCK2R with a high specificity, subsequently internalized via a mechanism involving recruitment of ß-arrestins, clathrin-coated pits, and dynamin and were directed to lysosomes. Binding and internalization of MG-IONP-DY647 were dependent on the density of the ligand at the nanoparticle surface and were slowed down relative to free ligand. Trafficking of CCK2R internalized with the nanoparticles was slightly modified relative to CCK2R internalized in response to free ligand. Application of an alternating magnetic field to cells containing MG-IONP-DY647 induced apoptosis and cell death through a lysosomal death pathway, demonstrating that cell death is triggered even though nanoparticles of low thermal power are internalized in minute amounts by the cells. Together with pioneer findings using iron oxide nanoparticles targeting tumoral cells expressing epidermal growth factor receptor, these data represent a solid basis for future studies aiming at establishing the proof-of-concept of nanotherapy of cancers using ligand-grafted magnetic nanoparticles specifically internalized via cell surface receptors.

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RESUMEN

In this work, a straightforward aqueous synthesis for mass production (up to 20 g) of uniform and crystalline magnetite nanoparticles with core sizes between 20 and 30 nm, which are the optimum nanoparticle core sizes for hyperthermia applications, is proposed. Magnetic and heating properties have been analyzed showing very high saturation magnetization and magnetic heating values. To stabilize the naked magnetite nanocrystals at physiological pH and increase their circulation time in blood, they have been covalently coated with carboxymethyl dextran, a biocompatible polymer. The influence of this superficial modification on the magnetic and heating properties has been studied showing that these biocompatible magnetic nanocrystals maintain high saturation magnetization values, good colloidal stability and hyperthermia properties in the presence of the polymeric external layer. These particles, suitably functionalized, could be used to selectively kill cancer cells under a moderate alternating magnetic field (44 mT and 70 kHz).