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The current study focuses on the synthesis via combustion of dysprosium-doped cobalt ferrites that were subsequently physicochemically analyzed in terms of morphological and magnetic properties. Three types of doped nanoparticles were prepared containing different Dy substitutions and coated with HPGCD for higher dispersion properties and biocompatibility, and were later submitted to biological tests in order to reveal their potential anticancer utility. Experimental data obtained through FTIR, XRD, SEM and TEM confirmed the inclusion of Dy3+ ions in the nanoparticles' structure. The size of the newly formed nanoparticles ranged between 20 and 50 nm revealing an inverse proportional relationship with the Dy content. Magnetic studies conducted by VSM indicated a decrease in remanent and saturation mass magnetization, respectively, in Dy-doped nanoparticles in a direct proportionality with the Dy content; the decrease was further amplified by cyclodextrin complexation. Biological assessment in the presence/absence of red light revealed a significant cytotoxic activity in melanoma (A375) and breast (MCF-7) cancer cells, while healthy keratinocytes (HaCaT) remained generally unaffected, thus revealing adequate selectivity. The investigation of the underlying cytotoxic molecular mechanism revealed an apoptotic process as indicated by nuclear fragmentation and shrinkage, as well as by Western blot analysis of caspase 9, p53 and cyclin D1 proteins. The anticancer activity for all doped Co ferrites varied was in a direct correlation to their Dy content but without being affected by the red light irradiation.
Assuntos
Antineoplásicos , Neoplasias da Mama , Melanoma , Nanopartículas , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Células MCF-7 , Nanopartículas/química , Luz , Antineoplásicos/farmacologia , Antineoplásicos/metabolismo , Melanoma/tratamento farmacológicoRESUMO
Raman nanoparticle probes are a potent class of optical labels for the interrogation of pathological and physiological processes in cells, bioassays, and tissues. Herein, we review the recent advancements in fluorescent and Raman imaging using oligodeoxyribonucleotide (ODN)-based nanoparticles and nanostructures, which show promise as effective tools for live-cell analysis. These nanodevices can be used to investigate a vast number of biological processes occurring at various levels, starting from those involving organelles, cells, tissues, and whole living organisms. ODN-based fluorescent and Raman probes have contributed to the achievement of significant advancements in the comprehension of the role played by specific analytes in pathological processes and have inaugurated new possibilities for diagnosing health conditions. The technological implications that have emerged from the studies herein described could open new avenues for innovative diagnostics aimed at identifying socially relevant diseases like cancer through the utilization of intracellular markers and/or guide surgical procedures based on fluorescent or Raman imaging. Particularly complex probe structures have been developed within the past five years, creating a versatile toolbox for live-cell analysis, with each tool possessing its own strengths and limitations for specific studies. Analyzing the literature reports in the field, we predict that the development of ODN-based fluorescent and Raman probes will continue in the near future, disclosing novel ideas on their application in therapeutic and diagnostic strategies.
Assuntos
Nanopartículas , Nanoestruturas , Ácidos Nucleicos , Análise Espectral Raman/métodos , Nanoestruturas/química , Corantes Fluorescentes/química , Imagem Molecular/métodos , Sondas de Ácido NucleicoRESUMO
Targeted nanocarriers could reach new levels of drug delivery, bringing new tools for personalized medicine. It is known that cancer cells overexpress folate receptors on the cell surface compared to healthy cells, which could be used to create new nanocarriers with specific targeting moiety. In addition, magnetic nanoparticles can be guided under the influence of an external magnetic field in different areas of the body, allowing their precise localization. The main purpose of this paper was to decorate the surface of magnetic nanoparticles with poly(2-hydroxyethyl methacrylate) (PHEMA) by surface-initiated atomic transfer radical polymerization (SI-ATRP) followed by covalent bonding of folic acid to side groups of the polymer to create a high specificity magnetic nanocarrier with increased internalization capacity in tumor cells. The biocompatibility of the nanocarriers was demonstrated by testing them on the NHDF cell line and folate-dependent internalization capacity was tested on three tumor cell lines: MCF-7, HeLa and HepG2. It has also been shown that a higher concentration of folic acid covalently bound to the polymer leads to a higher internalization in tumor cells compared to healthy cells. Last but not least, magnetic resonance imaging was used to highlight the magnetic properties of the functionalized nanoparticles obtained.
Assuntos
Ácido Fólico/química , Nanopartículas de Magnetita/química , Poli-Hidroxietil Metacrilato/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Células HeLa , Células Hep G2 , Humanos , Células MCF-7 , Tamanho da Partícula , PolimerizaçãoRESUMO
A series of neutral mononuclear lanthanide complexes [Ln(HL)2(NO3)3] (Ln = La, Ce, Nd, Eu, Gd, Dy, Ho) with rigid bidentate ligand, HL (4'-(1H-imidazol-1-yl)biphenyl-4-carboxylic acid) were synthesized under solvothermal conditions. The coordination compounds have been characterized by infrared spectroscopy, thermogravimetry, powder X-ray diffraction and elemental analysis. According to X-ray diffraction, all the complexes are a series of isostructural compounds crystallized in the P2/n monoclinic space group. Additionally, solid-state luminescence measurements of all complexes show that [Eu(HL)2(NO3)3] complex displays the characteristic emission peaks of Eu(III) ion at 593, 597, 615, and 651 nm.
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Mesitylene was used as a core in seven new tritopic nitrogen containing linkers. Three of the linkers, each containing three nitrile groups, were obtained through Suzuki, Sonogashira and Heck-type coupling reactions. Next, these were converted to tetrazol-5-yl moieties by the cycloaddition of sodium azide to the nitrile functionalities. The last linker, containing three 1,2,3-triazol-4-yl moieties, was synthesized by the Huisgen cycloaddition of phenyl azide to the corresponding alkyne. The latter was obtained via a Corey-Fuchs reaction sequence from the previously reported formyl derivative. As the proof of concept for their potential in MOF design, one of the nitriles was used to build an Ag-based network.
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New metal-organic frameworks (MOF) with lanthanum(III), cerium(III), neodymium(III), europium(III), gadolinium(III), dysprosium(III), and holmium(III)] and the ligand precursor 1,3,5-tris(4-carboxyphenyl)-2,4,6-trimethylbenzene (H3L) were synthesized under solvothermal conditions. Single crystal x-ray analysis confirmed the formation of three-dimensional frameworks of [LnL(H2O)2]n·xDMF·yH2O for Ln = La, Ce, and Nd. From the nitrogen sorption experiments, the compounds showed permanent porosity with Brunauer-Emmett-Teller (BET) surface areas of about 400 m2/g, and thermal stability up to 500 °C. Further investigations showed that these Ln-MOFs exhibit catalytic activity, paving the way for potential applications within the field of catalysis.
Assuntos
Elementos da Série dos Lantanídeos/química , Luminescência , Estruturas Metalorgânicas/química , Modelos Moleculares , Naftóis/química , Compostos Organometálicos/química , Acilação , Adsorção , Catálise , Elementos da Série dos Lantanídeos/metabolismo , Estruturas Metalorgânicas/metabolismo , Naftóis/metabolismo , Compostos Organometálicos/metabolismo , PorosidadeRESUMO
An important and well-designed solution to overcome some of the problems associated with new drugs is provided by the molecular encapsulation of the drugs in the cyclodextrins (CDs) cavity, yielding corresponding inclusion complexes (ICs). These types of non-covalent complexes are of current interest to the pharmaceutical industry, as they improve the solubility, stability and bioavailability of the guest molecules. This review highlights several methods for cyclodextrin ICs preparation and characterization, focusing mostly on the mass spectrometry (MS) studies that have been used for the detection of noncovalent interactions of CDs inclusion complexes and binding selectivity of guest molecules with CDs. Furthermore, the MS investigations of several ICs of the CD with antifungal, antioxidants or fluorescent dyes are presented in greater details, pointing out the difficulties overcome in the analysis of this type of compounds.
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Química Farmacêutica/métodos , Ciclodextrinas/análise , Espectrometria de Massas , SolubilidadeRESUMO
Generally, NSAIDs are weakly soluble in water and contain both hydrophilic and hydrophobic groups. One of the most widely used NSAIDs is ibuprofen, which has a poor solubility and high permeability profile. By creating dynamic, non-covalent, water-soluble inclusion complexes, cyclodextrins (CDs) can increase the dissolution rate of low aqueous solubility drugs, operating as a drug delivery vehicle, additionally contributing significantly to the chemical stability of pharmaceuticals and to reducing drug-related irritability. In order to improve the pharmacological and pharmacokinetics profile of ibuprofen, new thiazolidin-4-one derivatives of ibuprofen (4b, 4g, 4k, 4m) were complexed with ß-CD, using co-precipitation and freeze-drying. The new ß-CD complexes (ß-CD-4b, ß-CD-4g, ß-CD-4k, ß-CD-4m) were characterized using scanning electronic microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction and a phase solubility test. Using the AutoDock-VINA algorithm included in YASARA-structure software, we investigated the binding conformation of ibuprofen derivatives to ß-CD and measured the binding energies. We also performed an in vivo biological evaluation of the ibuprofen derivatives and corresponding ß-CD complexes, using analgesic/anti-inflammatory assays, as well as a release profile. The results support the theory that ß-CD complexes (ß-CD-4b, ß-CD-4g, ß-CD-4k, ß-CD-4m) have a similar effect to ibuprofen derivatives (4b, 4g, 4k, 4m). Moreover, the ß-CD complexes demonstrated a delayed release profile, which provides valuable insights into the drug-delivery area, focused on ibuprofen derivatives.
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Core-shell magnetic nanoparticle synthesis offers the opportunity to engineering their physical properties for specific applications when the intrinsic magnetic properties can be associated with other interesting ones. The purpose of this study was to design, synthesize, and characterize core-shell magnetic nanoparticles that mimic superoxide dismutase activity offering the possibility of guidance and therapeutic action. We proposed, for the first time, the synthesis and characterization of the nanocarriers comprised of magnetite nanoparticles functionalized with branched polyethyleneimine of low molecular weight (1.8â¯kDa) permitting the loading of the protocatechuic acid or its inclusion complex with anionic sulfobutylether-ß-cyclodextrin for active drug delivery, in order to combine the useful properties of the magnetite and the protocatechuic acid antioxidant effect. NMR and DSC analyses confirmed the formation of the inclusion complex between sulfobutylether-ß-cyclodextrin and protocatechuic acid, while structural and compositional analyses (FT-IR, TEM, XRD) revealed the synthesis of the multifunctional magnetic systems. Due to the possibility of being formulated as blood system injectable suspensions, antioxidant activity (using DPPH test) and cytotoxicity (using MTS assay on normal human dermal fibroblasts cells) were also measured, showing adequate properties to be used in biomedical applications. Moreover, we proposed a nanocarrier that would be able to load unstable active principles and with very low solubility in biological fluids to increase their biological ability.