RESUMO
Magnetic hyperthermia (MHT) is a promising approach for cancer therapy. However, a systematic MHT characterization as function of temperature on the therapeutic efficiency is barely analyzed. Here, we first perform comparative temperature-dependent analysis of the cobalt ferrite nanoparticles-mediated MHT effectiveness in two murine tumors models - breast (4T1) and colon (CT26) cancer in vitro and in vivo. The overall MHT killing capacity in vitro increased with the temperature and CT26 cells were more sensitive than 4T1 when heated to 43 °C. Well in line with the in vitro data, such heating cured non-metastatic CT26 tumors in vivo, while only inhibiting metastatic 4T1 tumor growth without improving the overall survival. High-temperature MHT (>47 °C) resulted in complete 4T1 primary tumor clearance, 25-40% long-term survival rates, and, importantly, more effective prevention of metastasis comparing to surgical extraction. Thus, the specific MHT temperature must be defined for each tumor individually to ensure a successful antitumor therapy.
Assuntos
Neoplasias da Mama/terapia , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/terapia , Magnetoterapia , Animais , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cobalto/química , Cobalto/farmacologia , Neoplasias do Colo/patologia , Modelos Animais de Doenças , Feminino , Compostos Férricos/química , Compostos Férricos/farmacologia , Humanos , Hipertermia Induzida/métodos , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/uso terapêutico , Camundongos , Metástase Neoplásica , TemperaturaRESUMO
Herein, we report a novel one-step solvothermal synthesis of magnetite nanoclusters (MNCs). In this report, we discuss the synthesis, structure, and properties of MNCs and contrast enhancement in T2-weighted MR images using magnetite nanoclusters. The effect of different organic acids, used as surfactants, on the size and shape of MNCs was investigated. The structure and properties of samples were determined by magnetic measurements, TGA, TEM, HRTEM, XRD, FTIR, and MRI. Magnetic measurements show that obtained MNCs have relatively high saturation magnetization values (65.1-81.5 emu/g) and dependence of the coercive force on the average size of MNCs was established. MNCs were transferred into an aqueous medium by Pluronic F-127, and T2-relaxivity values were determined. T2-Weighted MR phantom images clearly demonstrated that such magnetite nanoclusters can be used as contrast agents for MRI.
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Nowadays, magnetoelectric nanomaterials are on their way to finding wide applications in biomedicine for various cancer and neurological disease treatment, which is mainly restricted by their relatively high toxicity and complex synthesis. This study for the first time reports novel magnetoelectric nanocomposites of CoxFe3-xO4-BaTiO3 series with tuned magnetic phase structures, which were synthesized via a two-step chemical approach in polyol media. The magnetic CoxFe3-xO4 phases with x = 0.0, 0.5, and 1.0 were obtained by thermal decomposition in triethylene glycol media. The magnetoelectric nanocomposites were synthesized by the decomposition of barium titanate precursors in the presence of a magnetic phase under solvothermal conditions and subsequent annealing at 700 °C. X-ray diffraction revealed the presence of both spinel and perovskite phases after annealing with average crystallite sizes in the range of 9.0-14.5 nm. Transmission electron microscopy data showed two-phase composite nanostructures consisting of ferrites and barium titanate. The presence of interfacial connections between magnetic and ferroelectric phases was confirmed by high-resolution transmission electron microscopy. Magnetization data showed expected ferrimagnetic behavior and σs decrease after the nanocomposite formation. Magnetoelectric coefficient measurements after the annealing showed non-linear change with a maximum of 89 mV/cm*Oe with x = 0.5, 74 mV/cm*Oe with x = 0, and a minimum of 50 mV/cm*Oe with x = 0.0 core composition, that corresponds with the coercive force of the nanocomposites: 240 Oe, 89 Oe and 36 Oe, respectively. The obtained nanocomposites show low toxicity in the whole studied concentration range of 25-400 µg/mL on CT-26 cancer cells. The synthesized nanocomposites show low cytotoxicity and high magnetoelectric effects, therefore they can find wide applications in biomedicine.
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In this study, SrFe12-xNdxO19, where x = 0, 0.1, 0.2, 0.3, 0.4, and 0.5, was prepared using high-energy ball milling. The prepared samples were characterized by X-ray diffraction (XRD). Using the XRD results, a comparative analysis of crystallite sizes of the prepared powders was carried out by different methods (models) such as the Scherrer, Williamson-Hall (W-H), Halder-Wagner (H-W), and size-strain plot (SSP) method. All the studied methods prove that the average nanocrystallite size of the prepared samples increases by increasing the Nd concentration. The H-W and SSP methods are more accurate than the Scherer or W-H methods, suggesting that these methods are more suitable for analyzing the XRD spectra obtained in this study. The specific saturation magnetization (σs), the effective anisotropy constant (Keff), the field of magnetocrystalline anisotropy (Ha), and the field of shape anisotropy (Hd) for SrFe12-xNdxO19 (0 ≤ x ≤ 0.5) powders were calculated. The coercivity (Hc) increases (about 9% at x = 0.4) with an increasing degree of substitution of Fe3+ by Nd3+, which is one of the main parameters for manufacturing permanent magnets.
RESUMO
Enzymes conjugated to magnetic nanoparticles (MNPs) undergo changes in the catalytic activity of the non-heating low-frequency magnetic field (LFMF). We apply in silico simulations by molecular dynamics (MD) and in vitro spectroscopic analysis of the enzyme kinetics and secondary structure to study α-chymotrypsin (CT) conjugated to gold-coated iron oxide MNPs. The latter are functionalized by either carboxylic or amino group moieties to vary the points of enzyme attachment. The MD simulation suggests that application of the stretching force to the CT globule by its amino or carboxylic groups causes shrinkage of the substrate-binding site but little if any changes in the catalytic triad. Consistent with this, in CT conjugated to MNPs by either amino or carboxylic groups, LFMF alters the Michaelis-Menten constant but not the apparent catalytic constant k cat (= V max/[E]o). Irrespective of the point of conjugation to MNPs, the CT secondary structure was affected with nearly complete loss of α-helices and increase in the random structures in LFMF, as shown by attenuated total reflection Fourier transformed infrared spectroscopy. Both the catalytic activity and the protein structure of MNP-CT conjugates restored 3 h after the field exposure. We believe that such remotely actuated systems can find applications in advanced manufacturing, nanomedicine, and other areas.
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Redox-responsive and magnetic nanomaterials are widely used in tumor treatment separately, and while the application of their combined functionalities is perspective, exactly how such synergistic effects can be implemented is still unclear. This report investigates the internalization dynamics of magnetic redox-responsive nanoparticles (MNP-SS) and their cytotoxicity toward PC-3 and 4T1 cell lines. It is shown that MNP-SS synthesized by covalent grafting of polyethylene glycol (PEG) on the magnetic nanoparticle (MNP) surface via SS-bonds lose their colloidal stability and aggregate fully in a solution containing DTT, and partially in conditioned media, whereas the PEGylated MNP (MNP-PEG) without S-S linker control remains stable under the same conditions. Internalized MNP-SS lose the PEG shell more quickly, causing enhanced magnetic core dissolution and thus increased toxicity. This was confirmed by fluorescence microscopy using MNP-SS dual-labeled by Cy3 via labile disulfide, and Cy5 via a rigid linker. The dyes demonstrated a significant difference in fluorescence dynamics and intensity. Additionally, MNP-SS demonstrate quicker cellular uptake compared to MNP-PEG, as confirmed by TEM analysis. The combination of disulfide bonds, leading to faster dissolution of the iron oxide core, and the high-oxidative potential Fe3+ ions can synergically enhance oxidative stress in comparison with more stable coating without SS-bonds in the case of MNP-PEG. It decreases the cancer cell viability, especially for the 4T1, which is known for being sensitive to ferroptosis-triggering factors. In this work, we have shown the effect of redox-responsive grafting of the MNP surface as a key factor affecting MNP-internalization rate and dissolution with the release of iron ions inside cancer cells. This kind of synergistic effect is described for the first time and can be used not only in combination with drug delivery, but also in treatment of tumors responsive to ferroptosis.
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Solid solution AuFe nanoparticles were synthesized for the first time under ambient conditions by an adapted method previously established for the Fe3O4-Au core-shell morphology. These AuFe particles preserved the fcc structure of Au incorporated with paramagnetic Fe atoms. The metastable AuFe can be segregated by transformation into Janus Au/Fe particles with bcc Fe and fcc Au upon annealing. The ferromagnetic Fe was epitaxially grown on low index fcc Au planes. This preparation route delivers new perspective materials for magnetoplasmonics and biomedical applications and suggests the reconsideration of existing protocols for magnetite-gold core-shell synthesis.
RESUMO
The chemical synthesis of nanoparticles with a preassigned size and shape is important for an optimized performance in any application. Therefore, systematic monitoring of the synthesis is required for the control and detailed understanding of the nucleation and growth of the nanoparticles. Here, we study Fe3O4-Au hybrid nanoparticles in detail using probes of the reaction mixture during synthesis and their thorough characterization. The proposed approach eliminates the problem of repeatability and reproducibility of the chemical synthesis and was carried out using laboratory equipment (standard transmission electron microscopy, X-ray diffraction, and magnetometry) for typically 10 µL samples instead of, for example, a dedicated synthesis and inspection at a synchrotron radiation facility. From the three independent experimental techniques we extract the nanoparticle size at 12 stages of the synthesis. These diameters show identical trends and good quantitative agreement. Two consecutive processes occur during the synthesis of Fe3O4-Au nanoparticles, the nucleation and the growth of spherical Fe3O4 nanoparticles on the surface of Au seeds during the heating stage and their faceting towards octahedral shape during reflux. The final nanoparticles with sizes of 15 nm Fe3O4 and 4 nm Au exhibit superparamagnetic behavior at ambient temperature. These are high-quality, close to stoichiometric Fe3O4 nanocrystals with nearly volumetric magnetic behavior as confirmed by the presence of the Verwey transition. Understanding the processes occurring during the synthesis allows the nanoparticle size and shape to be adjusted, improving their capabilities in biomedical applications.
Assuntos
Óxido Ferroso-Férrico/química , Ouro/química , Nanopartículas de Magnetita/química , Óxido Ferroso-Férrico/síntese química , Tamanho da Partícula , Propriedades de SuperfícieRESUMO
Size-selected Fe3O4-Au hybrid nanoparticles with diameters of 6-44 nm (Fe3O4) and 3-11 nm (Au) were prepared by high temperature, wet chemical synthesis. High-quality Fe3O4 nanocrystals with bulk-like magnetic behavior were obtained as confirmed by the presence of the Verwey transition. The 25 nm diameter Fe3O4-Au hybrid nanomaterial sample (in aqueous and agarose phantom systems) showed the best characteristics for application as contrast agents in magnetic resonance imaging and for local heating using magnetic particle hyperthermia. Due to the octahedral shape and the large saturation magnetization of the magnetite particles, we obtained an extraordinarily high r 2-relaxivity of 495 mM-1·s-1 along with a specific loss power of 617 W·gFe -1 and 327 W·gFe -1 for hyperthermia in aqueous and agarose systems, respectively. The functional in vitro hyperthermia test for the 4T1 mouse breast cancer cell line demonstrated 80% and 100% cell death for immediate exposure and after precultivation of the cells for 6 h with 25 nm Fe3O4-Au hybrid nanomaterials, respectively. This confirms that the improved magnetic properties of the bifunctional particles present a next step in magnetic-particle-based theranostics.
RESUMO
High-quality, 25 nm octahedral-shaped Fe3O4 magnetite nanocrystals are epitaxially grown on 9 nm Au seed nanoparticles using a modified wet-chemical synthesis. These Fe3O4-Au Janus nanoparticles exhibit bulk-like magnetic properties. Due to their high magnetization and octahedral shape, the hybrids show superior in vitro and in vivo T2 relaxivity for magnetic resonance imaging as compared to other types of Fe3O4-Au hybrids and commercial contrast agents. The nanoparticles provide two functional surfaces for theranostic applications. For the first time, Fe3O4-Au hybrids are conjugated with two fluorescent dyes or the combination of drug and dye allowing the simultaneous tracking of the nanoparticle vehicle and the drug cargo in vitro and in vivo. The delivery to tumors and payload release are demonstrated in real time by intravital microscopy. Replacing the dyes by cell-specific molecules and drugs makes the Fe3O4-Au hybrids a unique all-in-one platform for theranostics.