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Magnetic bioactive glass-ceramics are biomaterials applied for magnetic hyperthermia in bone cancer treatment, thereby treating the bone tumor besides regenerating the damaged bone. However, combining high bioactivity and high saturation magnetization remains a challenge since the thermal treatment step employed to grow magnetic phases is also related to loss of bioactivity. Here, we propose a new nanocomposite made of superparamagnetic iron oxide nanoparticles (SPIONs) dispersed in a sol-gel-derived bioactive glass matrix, which does not need any thermal treatment for crystallization of magnetic phases. The scanning and transmission electron microscopies, X-ray diffraction, and dynamic light scattering results confirm that the SPIONs are actually embedded in a nanosized glass matrix, thus forming a nanocomposite. Magnetic and calorimetric characterizations evidence their proper behavior for hyperthermia applications, besides evidencing inter-magnetic nanoparticle interactions within the nanocomposite. Bioactivity and in vitro characterizations show that such nanocomposites exhibit apatite-forming properties similar to the highly bioactive parent glass, besides being osteoinductive. This methodology is a new alternative to produce magnetic bioactive materials to which the magnetic properties only rely on the quality of the SPIONs used in the synthesis. Thereby, these nanocomposites can be recognized as a new class of bioactive materials for applications in bone cancer treatment by hyperthermia.
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Hipertermia Induzida , Nanocompostos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Vidro/química , Nanopartículas Magnéticas de Óxido de Ferro , Fenômenos Magnéticos , Nanocompostos/químicaRESUMO
Composites of magnetite nanoparticles encapsulated with polymers attract interest for many applications, especially as theragnostic agents for magnetic hyperthermia, drug delivery, and magnetic resonance imaging. In this work, magnetite nanoparticles were synthesized by coprecipitation and encapsulated with different polymers (Eudragit S100, Pluronic F68, Maltodextrin, and surfactants) by nano spray drying technique, which can produce powders of nanoparticles from solutions or suspensions. Transmission and scanning electron microscopy images showed that the bare magnetite nanoparticles have 10.5 nm, and after encapsulation, the particles have approximately 1 µm, with size and shape depending on the material's composition. The values of magnetic saturation by SQUID magnetometry and mass residues by thermogravimetric analysis were used to characterize the magnetic content in the materials, related to their magnetite/polymer ratios. Zero-field-cooling and field-cooling (ZFC/FC) measurements showed how blocking temperatures of the powders of the composites are lower than that of bare magnetite, possibly due to lower magnetic coupling, being an interesting system to study magnetic interactions of nanoparticles. Furthermore, studies of cytotoxic effect, hydrodynamic size, and heating capacity for hyperthermia (according to the application of an alternate magnetic field) show that these composites could be applied as a theragnostic material for a non-invasive administration such as nasal.
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A ferrofluid with 1,2-Benzenediol-coated iron oxide nanoparticles was synthesized and physicochemically analyzed. This colloidal system was prepared following the typical co-precipitation method, and superparamagnetic nanoparticles of 13.5 nm average diameter, 34 emu/g of magnetic saturation, and 285 K of blocking temperature were obtained. Additionally, the zeta potential showed a suitable colloidal stability for cancer therapy assays and the magneto-calorimetric trails determined a high power absorption density. In addition, the oxidative capability of the ferrofluid was corroborated by performing the Fenton reaction with methylene blue (MB) dissolved in water, where the ferrofluid was suitable for producing reactive oxygen species (ROS), and surprisingly a strong degradation of MB was also observed when it was combined with H2O2. The intracellular ROS production was qualitatively corroborated using the HT-29 human cell line, by detecting the fluorescent rise induced in 2,7-dichlorofluorescein diacetate. In other experiments, cell metabolic activity was measured, and no toxicity was observed, even with concentrations of up to 4 mg/mL of magnetic nanoparticles (MNPs). When the cells were treated with magnetic hyperthermia, 80% of cells were dead at 43 °C using 3 mg/mL of MNPs and applying a magnetic field of 530 kHz with 20 kA/m amplitude.
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Coloides/química , Coloides/farmacologia , Hipertermia Induzida/métodos , Nanopartículas Magnéticas de Óxido de Ferro/química , Espécies Reativas de Oxigênio/metabolismo , Catecóis/química , Linhagem Celular , Coloides/síntese química , Citotoxinas/síntese química , Citotoxinas/química , Citotoxinas/farmacologia , Humanos , Concentração de Íons de Hidrogênio , Magnetismo , Microscopia Eletrônica de Transmissão , Oxidantes/síntese química , Oxidantes/química , Oxidantes/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura , Difração de Raios XRESUMO
Magnetic oxides are promising materials for alternative health diagnoses and treatments. The aim of this work is to understand the dependence of the heating power with the nanoparticle (NP) mean size, for the manganite composition La0.75Sr0.25MnO3 (LSMO)-the one with maximum critical temperature for the whole La/Sr ratio of the series. We have prepared four different samples, each one annealed at different temperatures, in order to produce different mean NP sizes, ranging from 26 nm up to 106 nm. Magnetization measurements revealed a FC-ZFC irreversibility and from the coercive field as function of temperature we determined the blocking temperature. A phase diagram was delivered as a function of the NP mean size and, based on this, the heating mechanism understood. Small NPs (26 nm) is heated up within the paramagnetic range of temperature (T>Tc), and therefore provide low heating efficiency; while bigger NPs are heated up, from room temperature, within the magnetically blocked range of temperature (T
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Although the three main phases of iron oxide - hematite, maghemite, and magnetite - exhibit superparamagnetic properties at the nanoscale, only maghemite and magnetite phases have been explored in magnetic bioactive glass-ceramics aimed at applications in cancer treatment by hyperthermia. In this work, it is reported for the first time the superparamagnetic properties of hematite nanocrystals grown in a 58S bioactive glass matrix derived from sol-gel synthesis. The glass-ceramics are based on the (100-x)(58SiO2-33CaO-9P2O5)-xFe2O3 system (x = 10, 20 and 30 wt%). A thermal treatment leads to the growth of hematite (α-Fe2O3) nanocrystals, conferring superparamagnetic properties to the glass-ceramics, which is enough to produce heat under an external alternating magnetic field. Besides, the crystallization does not inhibit materials bioactivity, evidenced by the formation of calcium phosphate onto the glass-ceramic surface upon soaking in simulated body fluid. Moreover, their cytotoxicity is similar to other magnetic bioactive glass-ceramics reported in the literature. Finally, these results suggest that hematite nanocrystals' superparamagnetic properties may be explored in multifunctional glass-ceramics applied in bone cancer treatment by hyperthermia allied to bone regeneration.
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Materiais Biocompatíveis , Nanopartículas , Cerâmica , Compostos Férricos , Vidro , Humanos , Hipertermia , Nanopartículas Magnéticas de Óxido de Ferro , Fenômenos MagnéticosRESUMO
Currently, antimicrobial photodynamic therapy (APDT) is limited to the local treatment of topical infections, and a platform that can deliver the photosensitizer to internal organs is highly desirable for non-local ones; SPIONs can be promising vehicles for the photosensitizer. This work reports an innovative application of methylene blue (MB)-superparamagnetic iron oxide nanoparticles (SPIONs). We report on the preparation, characterization, and application of MB-SPIONs for antimicrobial photodynamic therapy. When exposed to light, the MB photosensitizer generates reactive oxygen species (ROS), which cause irreversible damage in microbial cells. We prepare SPIONs by the co-precipitation method. We cover the nanoparticles with a double silica layer - tetraethyl orthosilicate and sodium silicate - leading to the hybrid material magnetite-silica-MB. We characterize the as-prepared SPIONs by Fourier transform infrared spectroscopy, powder X-ray diffraction, and magnetic measurements. We confirm the formation of magnetite using powder X-ray diffraction data. We use the Rietveld method to calculate the average crystallite size of magnetite as being 14 nm. Infrared spectra show characteristic bands of ironoxygen as well as others associated with silicate groups. At room temperature, the nanocomposites present magnetic behavior due to the magnetite core. Besides, magnetite-silica-MB can promote ROS formation. Thus, we evaluate the photodynamic activity of Fe3O4-silica-MB on Escherichia coli. Our results show the bacteria are completely eradicated following photodynamic treatment depending on the MB release time from SPIONs and energy dose. These findings encourage us to explore the use of magnetite-silica-MB to fight internal infections in preclinical assays.
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Infecções por Escherichia coli/tratamento farmacológico , Luz , Nanopartículas Magnéticas de Óxido de Ferro/química , Azul de Metileno/química , Humanos , Microscopia Eletrônica de Varredura , Fotoquimioterapia/métodos , Difração de Pó , Estudo de Prova de Conceito , Espectrometria por Raios X , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
Aim: The primary goal of this work was to synthesize low-cost superparamagnetic iron oxide nanoparticles (SPIONs) with the aid of coconut water and evaluate the ability of macrophages to internalize them. Our motivation was to determine potential therapeutic applications in drug-delivery systems associated with magnetic hyperthermia. Materials & methods: We used the following characterization techniques: x-ray and electron diffractions, electron microscopy, spectrometry and magnetometry. Results: The synthesized SPIONs, roughly 4 nm in diameter, were internalized by macrophages, likely via endocytic/phagocytic pathways. They were randomly distributed throughout the cytoplasm and mainly located in membrane-bound compartments. Conclusion: Nanoparticles presented an elevated intrinsic loss power value and were not cytotoxic to mammalian cells. Thus, we suggest that low-cost SPIONs have great therapeutic potential.
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Compostos Férricos/uso terapêutico , Química Verde/métodos , Macrófagos/metabolismo , Nanopartículas de Magnetita/uso terapêutico , Animais , Sistemas de Liberação de Medicamentos , Compostos Férricos/farmacocinética , Química Verde/economia , Hipertermia Induzida/métodos , Nanopartículas de Magnetita/análise , Nanopartículas de Magnetita/ultraestrutura , Camundongos , Células RAW 264.7RESUMO
Superparamagnetic magnetite nanoparticles have been synthesized by a highly reproducible polyvinyl alcohol (PVA)-based modified sol-gel process using water as the only solvent. The synthesis method has proven to be effective, time and cost saving and environmental friendly, resulting in PVA-coated magnetite nanoparticles as direct product from the synthesis, without any special atmosphere or further thermal treatment. X-ray diffraction and transmission electron microscopy revealed that the biocompatible PVA-coating prevents the nanoparticle agglomeration, giving rise to spherical crystals with sizes of 6.8nm (as-cast) and 9.5nm (heat treated) with great control over size and shape with narrow size distribution. Complementary compositional and magnetic characterizations were employed in order to study the surface chemistry and magnetic behavior of the samples, respectively. Cytotoxicity endpoints including no observed adverse effect concentration (NOAEC), 50% lethal concentration (LC50) and total lethal concentration (TLC) of the tested materials on cell viability were determined after 3, 24 and 48h of exposure. The PVA coating improved the biocompatibility of the synthesized magnetite nanoparticles showing good cell viability and low cytotoxicity effects on the MTT assay performed on BHK cells. Preliminary assessment of nanoparticles in vivo effects, performed after 48h on Balb/c mice, exposed to a range of different sub-lethal doses, showed their capacity to penetrate in liver and kidneys with no significant morphological alterations in both organs.
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Nanopartículas de Magnetita , Animais , Magnetismo , Microscopia Eletrônica de Transmissão , Álcool de Polivinil , Difração de Raios XRESUMO
Mesoporous materials with superparamagnetic properties were successfully synthesized by two different methods: direct incorporation (DI) and wet impregnation (WI). The synthetized solids were evaluated as host of drugs for delivery systems and their physicochemical properties were characterized by XRD, ICP, N2 adsorption-desorption, spectroscopies of UV-Vis DR, FT-IR and their magnetic properties were measured. Indomethacin (IND) was incorporated into the materials and the kinetic of the release profiles was studied by applying the Pepas and Sahlin model. In this sense, materials modified by DI, particularly that with hydrothermal treatment, showed the higher adsorption capacity and slower release rate. This behavior could be associated to the synthesis method used that allowed a high percentage of silanol groups available in the solids surface, which can interact with the IND molecule. This feature coupled with the superparamagnetic behavior; make these materials very interesting for drug delivery systems.
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Dióxido de Silício/química , Liberação Controlada de Fármacos , Nanopartículas de Magnetita , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
In this research work, DEXTRAN- and polyethylene glycol (PEG)-coated iron-oxide superparamagnetic nanoparticles were synthetized and their cytotoxicity and biodistribution assessed. Well-crystalline hydrophobic Fe3 O4 SPIONs were formed by a thermal decomposition process with d = 18 nm and σ = 2 nm; finally, the character of SPIONs was changed to hydrophilic by a post-synthesis procedure with the functionalization of the SPIONs with PEG or DEXTRAN. The nanoparticles present high saturation magnetization and superparamagnetic behavior at room temperature, and the hydrodynamic diameters of DEXTRAN- and PEG-coated SPIONs were measured as 170 and 120 nm, respectively. PEG- and DEXTRAN-coated SPIONs have a Specific Power Absorption SPA of 320 and 400 W/g, respectively, in an ac magnetic field with amplitude of 13 kA/m and frequency of 256 kHz. In vitro studies using VERO and MDCK cell lineages were performed to study the cytotoxicity and cell uptake of the SPIONs. For both cell lineages, PEG- and DEXTRAN-coated nanoparticles presented high cell viability for concentrations as high as 200 µg/mL. In vivo studies were conducted using BALB/c mice inoculating the SPIONs intravenously and exposing them to the presence of an external magnet located over the tumour. It was observed that the amount of PEG-coated SPIONs in the tumor increased by up to 160% when using the external permanent magnetic as opposed to those animals that were not exposed to the external magnetic field.