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Neurodegenerative diseases involve progressive neuronal death. Traditional treatments often struggle due to solubility, bioavailability, and crossing the Blood-Brain Barrier (BBB). Nanoparticles (NPs) in biomedical field are garnering growing attention as neurodegenerative disease drugs (NDDs) carrier to the central nervous system. Here, we introduced computational and experimental analysis. In the computational study, a specific IFPTML technique was used, which combined Information Fusion (IF) + Perturbation Theory (PT) + Machine Learning (ML) to select the most promising Nanoparticle Neuronal Disease Drug Delivery (N2D3) systems. For the application of IFPTML model in the nanoscience, NANO.PTML is used. IF-process was carried out between 4403 NDDs assays and 260 cytotoxicity NP assays conducting a dataset of 500,000 cases. The optimal IFPTML was the Decision Tree (DT) algorithm which shown satisfactory performance with specificity values of 96.4% and 96.2%, and sensitivity values of 79.3% and 75.7% in the training (375k/75%) and validation (125k/25%) set. Moreover, the DT model obtained Area Under Receiver Operating Characteristic (AUROC) scores of 0.97 and 0.96 in the training and validation series, highlighting its effectiveness in classification tasks. In the experimental part, two samples of NPs (Fe3O4_A and Fe3O4_B) were synthesized by thermal decomposition of an iron(III) oleate (FeOl) precursor and structurally characterized by different methods. Additionally, in order to make the as-synthesized hydrophobic NPs (Fe3O4_A and Fe3O4_B) soluble in water the amphiphilic CTAB (Cetyl Trimethyl Ammonium Bromide) molecule was employed. Therefore, to conduct a study with a wider range of NP system variants, an experimental illustrative simulation experiment was performed using the IFPTML-DT model. For this, a set of 500,000 prediction dataset was created. The outcome of this experiment highlighted certain NANO.PTML systems as promising candidates for further investigation. The NANO.PTML approach holds potential to accelerate experimental investigations and offer initial insights into various NP and NDDs compounds, serving as an efficient alternative to time-consuming trial-and-error procedures.
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Nanopartículas , Nanopartículas/química , Aprendizaje Automático , Algoritmos , Animales , Enfermedades Neurodegenerativas/tratamiento farmacológico , Neurociencias/métodos , Simulación por Computador , Humanos , Barrera Hematoencefálica/metabolismo , Sistemas de Liberación de Medicamentos/métodos , Portadores de Fármacos/químicaRESUMEN
We present results concerning the fabrication of a new magnetorheological fluid with FeCo magnetic nanoparticles (NPs) as magnetic fillers. These NPs have been fabricated by using the chemical reduction technique and show a pure crystalline phase with size ranging among 30-50 nm and high magnetization, 212 ± 2 A m2 kg-1. They agglomerate due to the strong magnetic dipolar interaction among them. These FeCo nanoparticles were used to synthesize a magnetorheological fluid by using oleic acid as surfactant, mineral oil as carrier liquid and Aerosil 300 as additive to control the viscosity of the fluid. The synthesized fluid showed a strong magnetorheological response with increasing shear stress values as the magnetic field intensity increases. Thus, we have measured a superior performance up to 616.7 kA m-1, with a yield stress value of 2729 Pa, and good reversibility after demagnetization process. This value competes with the best ones reported in the most recent literature. We have compared the obtained results with our previous reported ones by using high magnetization Fe NPs fabricated by the electrical explosion of wire method (Fe-EEW).
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AIM: The Specific Absorption Rate (SAR) is the key parameter to optimize the effectiveness of magnetic nanoparticles in magnetic hyperthermia. AC magnetometry arises as a powerful technique to quantify the SAR by computing the hysteresis loops' area. However, currently available devices produce quite limited magnetic field intensities, below 45mT, which are often insufficient to obtain major hysteresis loops and so a more complete and understandable magneticcharacterization. This limitation leads to a lack of information concerning some basic properties, like the maximum attainable (SAR) as a function of particles' size and excitation frequencies, or the role of the mechanical rotation in liquid samples. METHODS: To fill this gap, we have developed a versatile high field AC magnetometer, capable of working at a wide range of magnetic hyperthermia frequencies (100 kHz - 1MHz) and up to field intensities of 90mT. Additionally, our device incorporates a variable temperature system for continuous measurements between 220 and 380 K. We have optimized the geometrical properties of the induction coil that maximize the generated magnetic field intensity. RESULTS: To illustrate the potency of our device, we present and model a series of measurements performed in liquid and frozen solutions of magnetic particles with sizes ranging from 16 to 29 nm. CONCLUSION: We show that AC magnetometry becomes a very reliable technique to determine the effective anisotropy constant of single domains, to study the impact of the mechanical orientation in the SAR and to choose the optimal excitation parameters to maximize heating production under human safety limits.
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Hipertermia Inducida , Hipertermia , Humanos , Campos Magnéticos , Magnetismo , TemperaturaRESUMEN
Focusing on the uncontrolled discharge of organic dyes, a known threat to human health and aquatic ecosystems, this work employs a dual-functional catalyst approach, by immobilizing a synthesized bismuth sulfur iodide (BiSI) into a poly (vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) polymeric matrix for multifunctional water remediation. The resulting BiSI@PVDF nanocomposite membrane (NCM), with 20 wt% filler content, maintains a highly porous structure without compromising morphology or thermal properties. Demonstrating efficiency in natural pH conditions, the NCM removes nearly all Rhodamine B (RhB) within 1 h, using a combined sonophotocatalytic process. Langmuir and pseudo-second-order models describe the remediation process, achieving a maximum removal capacity (Qmax) of 72.2 mg/g. In addition, the combined sonophotocatalysis achieved a degradation rate ten and five times higher (0.026 min-1) than photocatalysis (0.002 min-1) and sonocatalysis (0.010 min-1). Furthermore, the NCM exhibits notable reusability over five cycles without efficiency losses and efficiencies always higher than 90%, highlighting its potential for real water matrices. The study underscores the suitability of BiSI@PVDF as a dual-functional catalyst for organic dye degradation, showcasing synergistic adsorption, photocatalysis, and sonocatalysis for water remediation.
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Bismuto , Colorantes , Nanocompuestos , Polivinilos , Rodaminas , Contaminantes Químicos del Agua , Purificación del Agua , Contaminantes Químicos del Agua/química , Nanocompuestos/química , Catálisis , Rodaminas/química , Bismuto/química , Colorantes/química , Purificación del Agua/métodos , Polivinilos/química , Polímeros de FluorocarbonoRESUMEN
In recent years, much effort has been invested into developing multifunctional drug delivery systems to overcome the drawbacks of conventional carriers. Magnetic nanoparticles are not generally used as carriers but can be functionalised with several different biomolecules and their size can be tailored to present a hyperthermia response, allowing for the design of multifunctional systems which can be active in therapies. In this work, we have designed a drug carrier nanosystem based on Fe3O4 nanoparticles with large heating power and 4-amino-2-pentylselenoquinazoline as an attached drug that exhibits oxidative properties and high selectivity against a variety of cancer malignant cells. For this propose, two samples composed of homogeneous Fe3O4 nanoparticles (NPs) with different sizes, shapes, and magnetic properties have been synthesised and characterised. The surface modification of the prepared Fe3O4 nanoparticles has been developed using copolymers composed of poly(ethylene-alt-maleic anhydride), dodecylamine, polyethylene glycol and the drug 4-amino-2-pentylselenoquinazoline. The obtained nanosystems were properly characterised. Their in vitro efficacy in colon cancer cells and as magnetic hyperthermia inductors was analysed, thereby leaving the door open for their potential application as multimodal agents.
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Nanosystems that simultaneously contain fluorescent and magnetic modules can offer decisive advantages in the development of new biomedical approaches. A biomaterial that enables multimodal imaging and contains highly efficient nanoheaters together with an intrinsic temperature sensor would become an archetypical theranostic agent. In this work, we have designed a magneto-luminescent system based on Fe3O4 NPs with large heating power and thermosensitive rhodamine (Rh) fluorophores that exhibits the ability to self-monitor the hyperthermia degree. Three samples composed of highly homogeneous Fe3O4 NPs of â¼25 nm and different morphologies (cuboctahedrons, octahedrons, and irregular truncated-octahedrons) have been finely synthesized. These NPs have been thoroughly studied in order to choose the most efficient inorganic core for magnetic hyperthermia under clinically safe radiofrequency. Surface functionalization of selected Fe3O4 NPs has been carried out using fluorescent copolymers composed of PMAO, PEG and Rh. Copolymers with distinct PEG tail lengths (5-20 kDa) and different Rh percentages (5, 10, and 25%) have been synthesized, finding out that the copolymer with 20 kDa PEG and 10% Rh provides the best coating for an efficient fluorescence with minimal aggregation effects. The optimized Fe3O4@Rh system offers very suitable fluorescence thermosensitivity in the therapeutic hyperthermia range. Additionally, this sample presents good biocompatibility and displays an excellent heating capacity within the clinical safety limits of the AC field (≈ 1000 W/g at 142 kHz and 44 mT), which has been confirmed by both calorimetry and AC magnetometry. Thus, the current work opens up promising avenues toward next-generation medical technologies.
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The main objective of the preparation of the Fe3-xGaxO4 (0.14 ≤ x ≤ 1.35) system was to further the knowledge of the magnetic response of Ga3+-doped magnetite for application as MRI contrast agents. With this purpose, monodisperse nanoparticles between 7 and 10 nm with different amounts of gallium were prepared from an optimized protocol based on thermal decomposition of metallo-organic precursors. Thorough characterization of the sample was conducted in order to understand the influence of gallium doping on the structural, morphological and magnetic properties of the Fe3-xGaxO4 system. X-ray diffraction and X-ray absorption near-edge structure measurements have proved the progressive incorporation of Ga in the spinel structure, with different occupations in both tetrahedral and octahedral sites. Magnetization measurements as a function of field temperature have shown a clear dependence of magnetic saturation on the gallium content, reaching an Ms value of 110 Am2 kg-1 at 5 K for x = 0.14 (significantly higher than bulk magnetite) and considerably decreasing for amounts above x = 0.57 of gallium. For this reason, nanoparticles with moderate Ga quantities were water-transferred by coating them with the amphiphilic polymer PMAO to further analyse their biomedical potential. Cytotoxicity assays have demonstrated that Fe3-xGaxO4@PMAO formulations with x ≤ 0.57, which are the ones with better magnetic response, are not toxic for cells. Finally, the effect of gallium doping on relaxivities has been analysed by measuring longitudinal (T1-1) and transverse (T1-1) proton relaxation rates at 1.4 T revealing that nanoparticles with x = 0.14 Ga3+ content present remarkable T2 contrast and the nanoparticles with x = 0.26 have great potential to act as dual T1-T2 contrast agents.
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Nanopartículas de MagnetitaRESUMEN
Among iron oxide phases, magnetite (Fe3O4) is often the preferred one for nanotechnological and biomedical applications because of its high saturation magnetization and low toxicity. Although there are several synthetic routes that attempt to reach magnetite nanoparticles (NPs), they are usually referred as "IONPs" (iron oxide NPs) due to the great difficulty in obtaining the monophasic and stoichiometric Fe3O4 phase. Added to this problem is the common increase of size/shape polydispersity when larger NPs (D > 20 nm) are synthesized. An unequivocal correlation between a nanomaterial and its properties can only be achieved by the production of highly homogeneous systems, which, in turn, is only possible by the continuous improvement of synthesis methods. There is no doubt that solving the compositional heterogeneity of IONPs while keeping them monodisperse remains a challenge for synthetic chemistry. Herein, we present a methodical optimization of the iron oleate decomposition method to obtain Fe3O4 single nanocrystals without any trace of secondary phases and with no need of postsynthetic treatment. The average dimension of the NPs, ranging from 20 to 40 nm, has been tailored by adjusting the total volume and the boiling point of the reaction mixture. Mössbauer spectroscopy and DC magnetometry have revealed that the NPs present a perfectly stoichiometric Fe3O4 phase. The high saturation magnetization (93 (2) A·m2/kg at RT) and the extremely sharp Verwey transition (at around 120 K) shown by these NPs have no precedent. Moreover, the synthesis method has been refined to obtain NPs with octahedral morphology and suitable magnetic anisotropy, which significantly improves the magnetic hyperthemia performance. The heating power of properly PEGylated nano-octahedrons has been investigated by AC magnetometry, confirming that the NPs present negligible dipolar interactions, which leads to an outstanding magnetothermal efficiency that does not change when the NPs are dispersed in environments with high viscosity and ionic strength. Additionally, the heat production of the NPs within physiological media has been directly measured by calorimetry under clinically safe conditions, reasserting the excellent adequacy of the system for hyperthermia therapies. To the best of our knowledge, this is the first time that such bulklike magnetite NPs (with minimal size/shape polydispersity, minor agglomeration, and exceptional heating power) are chemically synthesized.
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The currently existing magnetic hyperthermia treatments usually need to employ very large doses of magnetic nanoparticles (MNPs) and/or excessively high excitation conditions (H × f > 1010 A/m s) to reach the therapeutic temperature range that triggers cancer cell death. To make this anticancer therapy truly minimally invasive, it is crucial the development of improved chemical routes that give rise to monodisperse MNPs with high saturation magnetization and negligible dipolar interactions. Herein, we present an innovative chemical route to synthesize Zn-doped magnetite NPs based on the thermolysis of two kinds of organometallic precursors: (i) a mixture of two monometallic oleates (FeOl + ZnOl), and (ii) a bimetallic iron-zinc oleate (Fe3-y Zn y Ol). These approaches have allowed tailoring the size (10-50 nm), morphology (spherical, cubic, and cuboctahedral), and zinc content (Zn x Fe3-x O4, 0.05 < x < 0.25) of MNPs with high saturation magnetization (≥90 Am2/kg at RT). The oxidation state and the local symmetry of Zn2+ and Fe2+/3+ cations have been investigated by means of X-ray absorption near-edge structure (XANES) spectroscopy, while the Fe center distribution and vacancies within the ferrite lattice have been examined in detail through Mössbauer spectroscopy, which has led to an accurate determination of the stoichiometry in each sample. To achieve good biocompatibility and colloidal stability in physiological conditions, the Zn x Fe3-x O4 NPs have been coated with high-molecular-weight poly(ethylene glycol) (PEG). The magnetothermal efficiency of Zn x Fe3-x O4@PEG samples has been systematically analyzed in terms of composition, size, and morphology, making use of the latest-generation AC magnetometer that is able to reach 90 mT. The heating capacity of Zn0.06Fe2.9 4O4 cuboctahedrons of 25 nm reaches a maximum value of 3652 W/g (at 40 kA/m and 605 kHz), but most importantly, they reach a highly satisfactory value (600 W/g) under strict safety excitation conditions (at 36 kA/m and 125 kHz). Additionally, the excellent heating power of the system is kept identical both immobilized in agar and in the cellular environment, proving the great potential and reliability of this platform for magnetic hyperthermia therapies.
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Local heat generation from magnetic nanoparticles (MNPs) exposed to alternating magnetic fields can revolutionize cancer treatment. However, the application of MNPs as anticancer agents is limited by serious drawbacks. Foremost among these are the fast uptake and biodegradation of MNPs by cells and the unpredictable magnetic behavior of the MNPs when they accumulate within or around cells and tissues. In fact, several studies have reported that the heating power of MNPs is severely reduced in the cellular environment, probably due to a combination of increased viscosity and strong NP agglomeration. Herein, we present an optimized protocol to coat magnetite (Fe3O4) NPs larger than 20 nm (FM-NPs) with high molecular weight PEG molecules that avoid collective coatings, prevent the formation of large clusters of NPs and keep constant their high heating performance in environments with very different ionic strengths and viscosities (distilled water, physiological solutions, agar and cell culture media). The great reproducibility and reliability of the heating capacity of this FM-NP@PEG system in such different environments has been confirmed by AC magnetometry and by more conventional calorimetric measurements. The explanation of this behavior has been shown to lie in preserving as much as possible the magnetic single domain-type behavior of nearly isolated NPs. In vitro endocytosis experiments in a colon cancer-derived cell line indicate that FM-NP@PEG formulations with PEGs of higher molecular weight (20 kDa) are more resistant to endocytosis than formulations with smaller PEGs (5 kDa), showing quite large uptake mean-life (τ > 5 h) in comparison with other NP systems. The in vitro magnetic hyperthermia was performed at 21 mT and 650 kHz during 1 h in a pre-endocytosis stage and complete cell death was achieved 48 h posthyperthermia. These optimal FM-NP@PEG formulations with high resistance to endocytosis and predictable magnetic response will aid the progress and accuracy of the emerging era of theranostics.
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Agar , Nanopartículas de Magnetita/química , Polietilenglicoles/química , Agua , Calorimetría , Línea Celular Tumoral , Endocitosis/fisiología , Humanos , Hipertermia Inducida/métodos , MagnetometríaRESUMEN
Most studies on magnetic nanoparticle-based hyperthermia utilize iron oxide nanoparticles smaller than 20 nm, which are intended to have superparamagnetic behavior (SP-MNPs). However, the heating power of larger magnetic nanoparticles with non-fluctuating or fixed magnetic dipoles (F-MNPs) can be significantly greater than that of SP-MNPs if high enough fields (H > 15 mT) are used. But the synthesis of larger single nanocrystals of magnetite (Fe3O4) with a regular shape and narrow size distribution devoid of secondary phases remains a challenge. Iron oxide nanoparticles, grown over 25 nm, often present large shape and size polydispersities, twinning defects and a significant fraction of the wüstite-type (FeO) paramagnetic phase, resulting in degradation of magnetic properties. Herein, we introduce an improved procedure to synthesize monodisperse F-MNPs in the range of 25 to 50 nm with a distinct octahedral morphology and very crystalline magnetite phase. We unravel the subtle phase transformation that takes place during the synthesis by a thorough study in several non-optimized nanoparticles presenting a core-shell structure or composed of magnetite-type clusters embedded in a wüstite lattice. Optimized magnetite samples present a slight decrease in the saturation magnetization compared to bulk magnetite, which is successfully explained by the presence of Fe2+ vacancies. However, due to the high quality of these samples, AC magnetometry measurements have shown excellent specific absorption rates (>1000 W gFe3O4-1 at 40 mT and 300 kHz). Most importantly, the magnetic response and the hyperthermia performance of properly coated F-MNPs are kept basically unaltered in media with very different viscosities and ionic strength. Finally, using a physical model based on single magnetic domain approaches, we derive a novel connection between the octahedral shape and the high hyperthermia performance.
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Manganese/iron ferrite nanoparticles with different Mn2+/3+ doping grades have been prepared by a thermal decomposition optimized approach so as to ascertain the doping effect on magnetic properties and, especially, on the magnetic hyperthermia response. The oxidation state and interstitial position of Mn in the spinel structure is found to be critical. The particle size effect has also been studied by growing one of the prepared samples (from 10 to 15 nm in diameter) by a seed mediated growth mechanism. After analyzing the main structural and chemical parameters such as the Mn/Fe rate, crystalline structure, particle diameter, shape and organic coating, some Mn doping induced changes have been observed, such as the insertion of Mn2+ cations yielded more anisotropic shapes. Magnetic characterization, carried out by DC magnetometry (M(H), M(T)) and electron magnetic resonance (EMR) techniques, has shown interesting differences between samples with varying compositions. Lower Mn doping levels lead to larger saturation magnetization values, while an increase of the Mn content causes the decrease of the effective magnetic anisotropy constant at low T. The homogeneous magnetic response under applied magnetic fields, together with the great effect of nanoparticle size and shape in such a response, has been confirmed by the EMR analysis. Finally, a detailed magnetic hyperthermia analysis has demonstrated the large influence of NP size and shape on the magnetic hyperthermia response. The optimized Mn0.13Fe2.87O4_G sample with a diameter of 15 nm and slightly truncated octahedral shape is presented as an interesting candidate for future magnetic hyperthermia mediated biomedical treatments.
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With the aim of studying the influence of synthesis parameters in structural and magnetic properties of cobalt-doped magnetite nanoparticles, Fe3-xCoxO4 (0 < x < 0.15) samples were synthetized by thermal decomposition method at different reaction times (30-120 min). The Co ferrite nanoparticles are monodisperse with diameters between 6 and 11 nm and morphologies depending on reaction times, varying from spheric, cuboctahedral, to cubic. Chemical analysis and X-ray diffraction were used to confirm the composition, high crystallinity, and pure-phase structure. The investigation of the magnetic properties, both magnetization and electronic magnetic resonance, has led the conditions to improve the magnetic response of doped nanoparticles. Magnetization values of 86 emu·g-1 at room temperature (R.T.) have been obtained for the sample with the highest Co content and the highest reflux time. Magnetic characterization also displays a dependence of the magnetic anisotropy constant with the varying cobalt content.
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The two major limitations for nanoparticle based magnetic hyperthermia in theranostics are the delivery of a sufficient number of magnetic nanoparticles (MNPs) with high heating power to specific target cells and the residence time of the MNPs at the target location. Ferromagnetic or Ferrimagnetic single domain nanoparticles (F-MNPs), with a permanent magnetic dipole, produce larger magnetic and thermal responses than superparamagnetic nanoparticles (SP-MNPs) but also agglomerate more. MNP agglomeration degrades their heating potential due to dipolar interaction effects and interferes with specific targeting. Additionally, MNPs bound to cells are often endocytosed by the cells or, in vivo, cleared out by the immune system via uptake in macrophages. Here, we present a versatile approach to engineer inorganic-polymeric microdisks, loaded with biomolecules, fluorophores and Fe3O4 F-MNPs that solves both challenges. These microdisks deliver the F-MNPs efficiently, while controlling any undesirable agglomeration and dipolar interaction, while also rendering the F-MNPs endocytosis resistant. We show that these micro-devices are suitable carriers to transport a flat assembly of F-MNPs to the cell membrane unchanged, preserving the magnetic response of the MNPs in any biological environment. The F-MNPs concentration per microdisk and degree of MNP interaction are tunable. We demonstrate that the local heat generated in microdisks is proportional to the surface density of F-MNPs when attached to the cell membrane. The key innovation in the production of these microdisks is the fabrication of a mushroom-shaped photolithographic template that enables easy assembly of the inorganic film, polymeric multilayers, and MNP cargo while permitting highly efficient lift-off of the completed microdisks. During the harvesting of the flat microdisks, the supporting mushroom-shaped templates are sacrificed. These resulting magnetic hybrid microdisks are tunable and efficient devices for magnetothermal actuation and hyperthermia.
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Óxido Ferrosoférrico/química , Nanopartículas de Magnetita/química , Animales , Membrana Celular/metabolismo , Colorantes Fluorescentes/química , Células HEK293 , Hipocampo/citología , Hipocampo/metabolismo , Humanos , Hipertermia Inducida , Microscopía Confocal , Poliaminas/química , Polietilenos/química , Polímeros/química , Compuestos de Amonio Cuaternario/química , Ratas , Ratas Sprague-Dawley , Dióxido de Silicio/química , Ácidos Sulfónicos/química , Temperatura , TermometríaRESUMEN
To improve the selectivity of magnetic nanoparticles for tumor treatment by hyperthermia, Fe3O4 nanoparticles have been functionalized with a peptide of the type arginine-glycine-aspartate (RGD) following a "click" chemistry approach. The RGD peptide was linked onto the previously coated nanoparticles in order to target αvß3 integrin receptors over-expressed in angiogenic cancer cells. Different coatings have been analyzed to enhance the biocompatibility of magnetic nanoparticles. Monodispersed and homogeneous magnetite nanoparticles have been synthesized by the seed growth method and have been characterized using X-ray diffraction, thermogravimetric analysis, infrared spectroscopy, transmission electron microscopy and magnetic measurements. The magnetic hyperthermia efficiency of the nanoparticles has also been investigated and cytotoxicity assays have been perfomed for functionalized nanoparticles.
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Biomarcadores de Tumor/metabolismo , Óxido Ferrosoférrico/química , Hipertermia Inducida , Integrina alfaVbeta3/metabolismo , Nanopartículas de Magnetita/administración & dosificación , Oligopéptidos/química , Animales , Biomarcadores de Tumor/genética , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Chlorocebus aethiops , Expresión Génica , Humanos , Integrina alfaVbeta3/genética , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/ultraestructura , Unión Proteica , Células VeroRESUMEN
Thiosemicarbazones and their metal derivatives have long been screened as antitumor agents, and their interactions with DNA have been analysed. Herein, we describe the synthesis and characterization of compounds containing [CuL]+ entities (HL = pyridine-2-carbaldehyde thiosemicarbazone) and adenine, cytosine or 9-methylguanine, and some of their corresponding nucleotides. For the first time, crystal structures of adenine- and 9-methylguanine-containing thiosemicarbazone complexes are reported. To the best of our knowledge, the first study on the affinity thiosemicarbazone-RNA is also provided here. Experimental and computational studies have shown that [CuL(OH2)]+ entities at low concentration intercalate into dsRNA poly(rA)·poly(rU) through strong hydrogen bonds involving uracil residues and π-π stacking interactions. In fact, noncovalent interactions are present both in the solid state and in solution. This behaviour diverges from that observed with DNA duplexes and creates an optimistic outlook in achieving selective binding to RNA for subsequent possible medical applications.
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This work reports important advances in the study of magnetic nanoparticles (MNPs) related to their application in different research fields such as magnetic hyperthermia. Nanotherapy based on targeted nanoparticles could become an attractive alternative to conventional oncologic treatments as it allows a local heating in tumoral surroundings without damage to healthy tissue. RGD-peptide-conjugated MNPs have been designed to specifically target αVß3 receptor-expressing cancer cells, being bound the RGD peptides by "click chemistry" due to its selectivity and applicability. The thermal decomposition of iron metallo-organic precursors yield homogeneous Fe3O4 nanoparticles that have been properly functionalized with RGD peptides, and the preparation of magnetic fluids has been achieved. The nanoparticles were characterized by transmission electron microscopy (TEM), vibrating sample magnetometry (VSM), electron magnetic resonance (EMR) spectroscopy and magnetic hyperthermia. The nanoparticles present superparamagnetic behavior with very high magnetization values, which yield hyperthermia values above 500 W/g for magnetic fluids. These fluids have been administrated to rats, but instead of injecting MNP fluid directly into liver tumors, intravascular administration of MNPs in animals with induced colorectal tumors has been performed. Afterwards the animals were exposed to an alternating magnetic field in order to achieve hyperthermia. The evolution of an in vivo model has been described, resulting in a significant reduction in tumor viability.
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Monodispersed Fe3O4 nanoparticles have been synthesized by a thermal decomposition method based on the seeded-growth technique, achieving size tunable nanoparticles with high crystallinity and high saturation magnetization. EMR spectroscopy becomes a very efficient complementary tool to determine the fine details of size distributions of MNPs and even to estimate directly the size in a system composed of a given type of magnetic nanoparticles. The size and size dispersity affect directly the efficiency of MNPs for hyperthermia and EMR provides a direct evaluation of these characteristics almost exactly in the same preparation and with the same concentration as used in hyperthermia experiments. The correlation observed between the Specific Absorption Rate (SAR) and the effective gyromagnetic factor (geff) is extremely remarkable and renders a way to assess directly the heating capacity of a MNP system.
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PURPOSE: To evaluate, in an experimental model, the reliability of MRI for determining whether a higher iron concentration was obtained in tumor tissue than in normal liver parenchyma after intra-arterial administration of Fe3O4 lipophilic nanoparticles. MATERIALS AND METHODS: WAG/RijCrl rats were inoculated in the left hepatic lobe with 25,000 syngeneic CC-531 colon adenocarcinoma cells, after which they were randomized into two groups: control (CG) and infused (IG). After confirming tumor induction, the IG rats received intra-arterial suspensions of Fe3O4 nanoparticles (2.6 mg) in Lipiodol® (0.15 mL). To calculate the iron concentration, [Fe], in the tumor and liver tissues of both groups of rats, measurements of signal intensity from the tumors, healthy liver tissue, and paravertebral muscles were made on a 1.5T MRI system in gradient-echo DP* and T2*-weighted sequences. In addition, samples were collected to quantify the [Fe] by inductively coupled plasma-mass spectrometry (ICP-MS), as well as for histological analysis. Statistical analysis was performed with non-parametric tests, and Bland-Altman plots were produced; P values <0.05 were considered significant. RESULTS: In the CG rats (n = 23), the mean [Fe] values estimated by MRI and ICP-MS were 13.2 µmol·g⻹ and 5.9 µmol·g⻹, respectively, in the tumors, and 19.0 µmol ·g⻹ and 11.7 µmol·g⻹, respectively, in the hepatic tissue. In the IG rats (n = 19), the values obtained by MRI and ICP-MS were 148.9 µmol·g⻹ and 9.4 µmol · g⻹, respectively, in the tumors, and 115.3 µmol·g⻹ and 11.6 µmol·g⻹, respectively, in the healthy liver tissue. The IG results revealed a clear disagreement between MRI and ICP-MS. In the comparative analysis between the groups regarding the [Fe] values obtained by ICP-MS, significant differences were found for the tumor samples (P < 0.001), but not for the hepatic tissue (P = 0.92). Under microscopy, scattered intravascular deposits of nanoparticles were observed, especially in the tumors. CONCLUSION: ICP-MS demonstrated significant uptake of exogenous iron in tumor tissue. MRI was useful for quantifying the [Fe] in the different tissues in the CG animals, but not in the IG animals. Although the irregular distribution of nanoparticles caused an important bias in the measurements obtained by MRI, the relative increase in iron content inside the tumor was suggested.
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Neoplasias Colorrectales/metabolismo , Neoplasias Hepáticas/metabolismo , Imagen por Resonancia Magnética/métodos , Nanopartículas de Magnetita/administración & dosificación , Espectrometría de Masas/métodos , Animales , Línea Celular Tumoral , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/irrigación sanguínea , Neoplasias Colorrectales/química , Arteria Hepática/metabolismo , Inyecciones Intravenosas , Hígado/química , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/irrigación sanguínea , Neoplasias Hepáticas/química , Nanopartículas de Magnetita/análisis , Nanopartículas de Magnetita/química , Masculino , Ratas , Estadísticas no Paramétricas , Distribución TisularRESUMEN
The crystal structures of [(ppy)Pd(mu-pz)](2) (ppy = 2-(2-pyridyl)phenyl, pz = pyrazol-1-yl) (1) and two different solvatomorphs of it, [(ppy)Pd(mu-pz)](2) x 1/2 CH(2)Cl(2) (2) and [(ppy)Pd(mu-pz)](2) x 1/2 CHCl(3) (3) have been elucidated by powder (1 and 2) and single crystal (3) X-ray diffraction. In all of them two molecules fit together following a very similar pattern forming a "dimer". All neutral dinuclear square-planar complexes having mu-pz or related bridges and planar aromatic ligands completing the coordination spheres found in the CSD show a similar arrangement to those observed in compounds 1-3, consisting of "interlocked dimers" following a herringbone-like pattern. A DFT study reveals the simultaneous action of pi,pi- and T-stacking interactions occurring as two sets of orthogonally oriented binding forces, as well as anagostic bonds overlapped with the latter.