Desarrollo de nano-agentes magnéticos para aplicación de hipertermia combinada con direccionamiento en el tratamiento selectivo del cáncer

La hipertermia magnética para el tratamiento de tumores es una alternativa terapéutica que se comenzó a estudiar hace ya muchos años, con el fin de encontrar una nueva herramienta para la terapia antitumoral menos agresiva que las ya conocidas. Se sintetizaron nanopartículas magnéticas de magnetita (Fe3O4) de aproximadamente 11 nm de diámetro mediante co-precipitación en medio acuoso. La superficie de las nanopartículas se funcionalizaron con 3aminopropil triethoxisilano (APTS) y ácido fólico (AF) para direccionamiento en células tumorales que sobreexpresen el receptor folato. Estas nanoestructuras tienen una disipación de calor caracterizada por un valor de SpecificAbsorptionRate (SAR) de 7.53 W/gFe para la termoterapia magnética bajo la acción de campos de radiofrecuencia en condiciones clínicas (100 kHz y 5 kA/m). La experimentación in vitro con la célula LM3 (Malignant neoplasms of the mouse mammary gland (NCIt: C21678). https://web.expasy.org/cellosaurus/CVCL_D269)permitió demostrar la disminución de la viabilidad celular un 6-7% luego del contacto con nanopartículas magnéticas durante 24 horas y posterior aplicación de campo magnético, respecto del control no expuesto al campo.Eje: Ciencia e Ingeniería de MaterialesInstituto de Física La Plat

On the microstructure and thermal stability of rapidly quenched Fe–B alloys in the intermediate composition range between the crystalline and amorphous states

The structure and the thermal stability of the Fe₀.₈₉B₀.₁₁ rapidly quenched alloy have been investigated. Transmission Mossbauer measurements were carried out as a function of temperature in the range from 148 K to 513 K. Room temperature x-ray diffraction and transmission and conversion-electron Mossbauer experiments, as well as 4.2 K spin-echo nuclear magnetic resonance measurements, were also performed after some selected thermal treatments for one hour between 523 K and 1273 K. Based on these experiments it is suggested that the alloy is inhomogeneous at nanoscopic scale and consists of a fine dispersion of a defective boride phase with an o-Fe₃B-like short-range order, embedded in an α-Fe matrix. This result gives support to the models which indicate phase separation in the amorphous phase with o-Fe3B short-range order prevailing in the hypereutectic iron concentration range. This phase was found to be less stable than the undefective one present in the less boron concentrated alloys. The transformation into the equilibrium phases, analyzed with an Arrhenius-type temperature dependence for the increase of the relative fraction of Fe₂B, led to an activation energy Ea = 1.38 ± 0.68 eV/atom.Facultad de Ciencias Exacta

Size dependent Cu dielectric function for plasmon spectroscopy: Characterization of colloidal suspension generated by fs laser ablation

Copper metal nanoparticles (Nps) have received increasing interest during the last years due to their potential applications in several fields of science and technology. Their optical properties depend on the characteristics of the dielectric function of the metal, their size, and the type of environment. The contribution of free and bound electrons on the dielectric function of copper Nps is analyzed as well as their influence on its plasmonic properties. The contribution of free electrons is corrected for particle size under 10 nm, introducing a term inversely proportional to the particle's radius in the damping constant. For bound electron contribution, interband transitions from the d-band to the conduction band are considered. For particles with sizes below 2 nm, the larger spacing between electronic energy levels must be taken into account by making the electronic density of states in the conduction band size-dependent. Considering these specific modifications, optical parameters and band energy values could be determined by fitting the bulk complex dielectric function. The obtained values were coefficient for bound electron contribution Kbulk = 2 × 1024, gap energy Eg = 1.95 eV, Fermi energy EF = 2.15 eV, and bound electrons damping constant γb = 1.15 × 1014 Hz. Based on the dielectric function determined in this way, experimental extinction spectra of colloid suspensions generated by ultrafast laser ablation of a solid copper target in liquids was fitted using the Drude-interband model and Mie's theory. Depending on the experimental conditions and liquid medium, the particles in the suspension may have nanometric or subnanometric core size and may be capped with a shell of oxide. From the fitting, it was possible to determine the structure and size distribution of spherical bare core and core-shell copper Nps in the nanometer-subnanometer size range. These results were compared with those obtained by standard microscopy techniques such as AFM and HRTEM. There is a very good agreement between the three techniques, showing that optical extinction spectroscopy (OES) is a good complementary technique to standard high resolution electron microscopy and AFM for sizing spherical nanometric-subnanometric Nps. OES has also the advantage of a very good measurement statistics, due to the large number of probed particles across the sample cell. Besides, it avoids coalescence effects since the measurement is made directly on the colloidal suspension.Fil: Santillán, Jesica María José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Ópticas. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Investigaciones Ópticas. Universidad Nacional de La Plata. Centro de Investigaciones Ópticas; ArgentinaFil: Videla, Fabian Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Ópticas. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Investigaciones Ópticas. Universidad Nacional de La Plata. Centro de Investigaciones Ópticas; ArgentinaFil: Fernández van Raap, Marcela Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; ArgentinaFil: Schinca, Daniel Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Ópticas. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Investigaciones Ópticas. Universidad Nacional de La Plata. Centro de Investigaciones Ópticas; ArgentinaFil: Scaffardi, Lucia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Ópticas. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Investigaciones Ópticas. Universidad Nacional de La Plata. Centro de Investigaciones Ópticas; Argentin

Magnetite nanoparticles coated with citric acid are not phytotoxic and stimulate soybean and alfalfa growth

In this work, the internalization and distribution of citric acid-coated magnetite nanoparticles (here, Fe3O4-NPs) in soybean and alfalfa tissues and their effects on plant growth were studied. Both legumes were germinated in pots containing an inert growing matrix (vermiculite) to which Hoagland solution without (control, C), with Fe3O4-NPs (50 and 100 mg iron L−1, NP50 and NP100), or with the same amount of soluble iron supplied as Fe-EDTA (Fe50, Fe100) was added once before sowing. Then, plants were watered with the standard nutrient solution. The observation of superparamagnetic signals in root tissues at harvest (26 days after emergence) indicated Fe3O4-NPs uptake by both legumes. A weak superparamagnetic signal was also present in the stems and leaves of alfalfa plants. These findings suggest that Fe3O4-NPs are readily absorbed but not translocated (soybean) or scarcely translocated (alfalfa) from the roots to the shoots. The addition of both iron sources resulted in increased root weight; however, only the addition of Fe3O4-NPs resulted in significantly higher root surface; shoot weight also increased significantly. As a general trend, chlorophyll content enhanced in plants grown in vermiculite supplemented with extra iron at pre-sowing; the greatest increase was observed with NP50. The only antioxidant enzyme significantly affected by our treatments was catalase, whose activity increased in the roots and shoots of both species exposed to Fe3O4-NPs. However, no symptoms of oxidative stress, such as increased lipid peroxidation or reactive oxygen species accumulation, were evidenced in any of these legumes. Besides, no evidence of cell membrane damage or cell death was found. Our results suggest that citric acid-coated Fe3O4-NPs are not toxic to soybean and alfalfa; instead, they behave as plant growth stimulators.Fil: Iannone, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Groppa, María Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Zawoznik, Myriam Sara. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Biológica. Cátedra de Química Biológica Vegetal; ArgentinaFil: Coral, Diego Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; ArgentinaFil: Fernández van Raap, Marcela Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; ArgentinaFil: Benavides, Maria Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentin

Stress-induced Gene Expression Sensing Intracellular Heating Triggered by Magnetic Hyperthermia

It is known that alternating magnetic field applications on eukaryotic cells loaded with single domain iron oxide nanoparticles result in high hyperthermic citotoxicity leading to cell dead. Although magnetic hyperthermia therapy for cancer tumours is being developed under this idea, some in vitro assays have shown controversial results indicating that alternating magnetic field triggers large apoptotic effect without significant culture-temperature increase. In agreement with these observations a huge lowering in nanoparticle specific heating rates, when going from the colloidal suspension to cell endosomes, together with cell death, has been reported. Here, we propose a new methodology to determine the occurrence of local heating in cells when alternating magnetic fields in the radiofrequency field range are applied to cell cultures holding very low iron oxide concentrations, being these concentrations insufficient to produce a global cell-culture temperature increase up to therapeutic values. To this end, human lung adenocarcinoma cells (A549 cell line) were transduced with a lentiviral vector encoding the expression of the enhanced green fluorescence protein, EGFP, under the action of the inducible human heat shock protein 70B promoter. This modified A549 cell line was incubated with aqueous suspensions of magnetite core nanoparticles (uncoated or covered with coating agents like citric acid or silicon oxide), and exposed to radiofrequency fields. The application of an alternating magnetic field to cell cultures loaded with nanoparticles resulted in no global temperature increase but EGFP expression. Stress-inducible gene expression scales with uptake and nanoparticle properties like saturation magnetization and heat dissipation efficiency. Our analysis demonstrates that EGFP expression is linked to a localized intracellular temperature increase.Fil: de Sousa, María Elisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; ArgentinaFil: Carrea, Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); ArgentinaFil: Mendoza Zélis, Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; ArgentinaFil: Muraca, Diego. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidade Estadual de Campinas; BrasilFil: Mykhaylyk, Olga. Technische Universitat Munchen; AlemaniaFil: Sosa, Yolanda Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata ; ArgentinaFil: Goya, Rodolfo Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata ; ArgentinaFil: Sánchez, Francisco Homero. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; ArgentinaFil: Dewey, Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); ArgentinaFil: Fernández van Raap, Marcela Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; Argentin

Selective contrast agents with potential to the earlier detection of tumors: Insights on synthetic pathways, physicochemical properties and performance in MRI assays

Magnetic iron oxide nanoparticles (MNPs) have been prepared and stabilized with three organic acids (tartaric, malic and ascorbic) in order to obtain biocompatible and water dispersible MNPs with potential to bind specifically to tumoral cancer cells. An in deep characterization was performed aiming to verify the presence and effect of the coating and stabilizer on MNPs surface. Besides the mechanisms followed by the different acids to bind MNPs were elucidated and used to justify the differences in the physicochemical properties of each formulation. Data related to characterization revealed that MNPs coated with ascorbic acid (MNPs-AA) resulted the most suitable in terms of their size, surface charge and stability along the time. Besides, ascorbic acid may be recognized by GLUTs receptors that are overexpressed in several kinds of tumoral cells. Therefore, MNPs-AA was selected to explore its performance in both MRI and in vitro assays using human colon cancer cells HCT 116. MRI experiments were performed in clinical equipment using a series of aqueous dispersions of MNPs-AA that were evaluated as T2 contrast agent. The T2- weighted images obtained as well as the calculated r2, indicated that MNPs-AA could act as efficient T2 contrast agent for MRI. Regarding in vitro assays, MNPs-AA did not alter the cellular function neither exert cytotoxicity using the three explored doses. The internalization of the nanoparticles on the cellular structure was confirmed quanti and qualitatively using atomic absorption spectroscopy and Prussian blue techniques respectively. From these results, it emerges that ascorbic acid coated-magnetite nanoparticles may be used as alternative contrast agent to avoid or minimize some toxicological issues related to the widely used gadolinium.Fil: Montiel Schneider, María Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; ArgentinaFil: Martin, Maria Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; ArgentinaFil: Coral, Diego Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; Argentina. Institución Universitaria CESMAG; ColombiaFil: Muraca, Diego. Universidade Estadual de Campinas; BrasilFil: Gentili, Claudia Rosana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; ArgentinaFil: Fernández van Raap, Marcela Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; ArgentinaFil: Lassalle, Verónica Leticia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentin

Quasi-static magnetic measurements to predict specific absorption rates in magnetic fluid hyperthermia experiments

In this work, the issue on whether dynamic magnetic properties of polydispersed magnetic colloids modeled using physical magnitudes derived from quasi-static magnetic measurement can be extrapolated to analyze specific absorption rate data acquired at high amplitudes and frequencies of excitation fields is addressed. To this end, we have analyzed two colloids of magnetite nanoparticles coated with oleic acid and chitosan in water displaying, under a radiofrequency field, high and low specific heat power release. Both colloids are alike in terms of liquid carrier, surfactant and magnetic phase composition but differ on the nanoparticle structuring. The colloid displaying low specific dissipation consists of spaced magnetic nanoparticles of mean size around 4.8 nm inside a large chitosan particle of 52.5 nm. The one displaying high specific dissipation consists of clusters of magnetic nanoparticles of mean size around 9.7 nm inside a chitosan particle of 48.6 nm. The experimental evaluation of Néel and Brown relaxation times (∼10−10 s and 10−4 s, respectively) indicate that the nanoparticles in both colloids magnetically relax by Néel mechanism. The isothermal magnetization curves analysis for this mechanism show that the magnetic nanoparticles behave in the interacting superparamagnetic regime. The specific absorption rates were determined calorimetrically at 260 kHz and up to 52 kA/m and were well modeled within linear response theory using the anisotropy density energy retrieved from quasi-static magnetic measurement, validating their use to predict heating ability of a given polydispersed particle suspension. Our findings provide new insight in the validity of quasi-static magnetic characterization to analyze the high frequency behavior of polydispersed colloids within the framework of the linear response and Wohlfarth theories and indicate that dipolar interactions play a key role being their strength larger for the colloid displaying higher dissipation, i.e., improving the heating efficiency of the nanoparticles for magnetic fluid hyperthermia.Fil: Coral, Diego Fernando. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Física; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; ArgentinaFil: Mendoza Zélis, Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; ArgentinaFil: de Sousa, María Elisa. Universidade Estadual de Campinas; Brasil. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Muraca, Diego. Universidade Estadual de Campinas; Brasil. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lassalle, Verónica Leticia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; ArgentinaFil: Nicolás, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; ArgentinaFil: Ferreira, María Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; ArgentinaFil: Fernández van Raap, Marcela Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; Argentin

Anticipating hyperthermic efficiency of magnetic colloids using a semi-empirical model: a tool to help medical decisions

Magnetic hyperthermia, a modality that uses radio frequency heating assisted with single-domain magnetic nanoparticles, is becoming established as a powerful oncological therapy. Much improvement in nanomaterials development, to enhance their heating efficiency by tuning the magnetic colloidal properties, has been achieved. However, methodological standardization to accurately and univocally determine the colloidal properties required to numerically reproduce a specific heating efficiency using analytical expressions still holds. Thus, anticipating the hyperthermic performances of magnetic colloids entails high complexity due to polydispersity, aggregation and dipolar interactions always present in real materials to a greater or lesser degree. Here, by numerically simulating the experimental results and using real biomedical aqueous colloids, we analyse and compare several approaches to reproduce experimental specific absorption rate values. Then, we show that the relaxation time, determined using a representative mean activation energy consistently derived from four independent experiments accurately reproduces experimental heating efficiencies. Moreover, the so-derived relaxation time can be used to extrapolate the heating performance of the magnetic nanoparticles to the other field conditions within the framework of the linear response theory. We thus present a practical tool that may truly aid the design of medical decisions.Facultad de Ciencias ExactasInstituto de Física La Plat

Mössbauer Effect Studies of Fe–Base Alloys during Mechanical Alloying and Grinding (Overview)

Mossbauer effect studies of mechanical alloying and mechanical grinding of Fe-B, Fe-Sn and Fe-TM-Al (TM = Ni, Cu), complemented by X-ray diffraction analysis are presented. Some of these systems (Fe-Sn) are especially suited for these type of research because the environments of both elements can be probed. In all cases powders were processed with a Retsch MM 2 horizontal vibratory mill under argon atmosphere. In Fe 1-x Sn x (0.15 ≤ x ≤ 0.40), the evolution of mechanical alloying with time and the dependence of the stationary state with composition were investigated. An intermediate superparamagnetic FeSn 2 state and a stationary bcc solid solution with composition fluctuations were inferred from the Mossbauer spectra. Solubility of tin into bcc iron was found to be extended up to a maximum of about 22 at.%. Pure powder mixtures of nominal composition Al 75 Ni 10 Fe 15 , Al 65 Ni 20 Fe 15 and Al 63 Cu 25 Fe 12 have been mechanically alloyed. Stable disordered crystalline phases were obtained after milling and, in some cases, the partial ordering of bcc structures induced by milling was observed. Further annealings did not produce structural changes but removed the remaining disorder. The characteristic quadrupole interaction parameters were obtained by Mossbauer spectroscopy. The evolution of Fe 2 B with grinding time was studied. The first milling stage was characterized by fragmentation and accumulation of strain. On further processing, segregation of α-Fe occurred while grain size reduction continued and strain was partially removed. For longer grinding times separation of α-Fe proceeded at an almost steady rate. Two additional experiments designed to reduce and increase oxygen contamination let us tentatively discard this element as the main responsible for the observed decomposition.Facultad de Ciencias Exacta

Stress-induced Gene Expression Sensing Intracellular Heating Triggered by Magnetic Hyperthermia

It is known that alternating magnetic field applications on eukaryotic cells loaded with single domain iron oxide nanoparticles result in high hyperthermic citotoxicity leading to cell dead. Although magnetic hyperthermia therapy for cancer tumours is being developed under this idea, some in vitro assays have shown controversial results indicating that alternating magnetic field triggers large apoptotic effect without significant culture-temperature increase. In agreement with these observations a huge lowering in nanoparticle specific heating rates, when going from the colloidal suspension to cell endosomes, together with cell death, has been reported. Here, we propose a new methodology to determine the occurrence of local heating in cells when alternating magnetic fields in the radiofrequency field range are applied to cell cultures holding very low iron oxide concentrations, being these concentrations insufficient to produce a global cell-culture temperature increase up to therapeutic values. To this end, human lung adenocarcinoma cells (A549 cell line) were transduced with a lentiviral vector encoding the expression of the enhanced green fluorescence protein, EGFP, under the action of the inducible human heat shock protein 70B promoter. This modified A549 cell line was incubated with aqueous suspensions of magnetite core nanoparticles (uncoated or covered with coating agents like citric acid or silicon oxide), and exposed to radiofrequency fields. The application of an alternating magnetic field to cell cultures loaded with nanoparticles resulted in no global temperature increase but EGFP expression. Stress-inducible gene expression scales with uptake and nanoparticle properties like saturation magnetization and heat dissipation efficiency. Our analysis demonstrates that EGFP expression is linked to a localized intracellular temperature increase.Facultad de Ciencias ExactasInstituto de Física La PlataFacultad de Ciencias MédicasInstituto de Investigaciones Bioquímicas de La Plat