RESUMEN
The present study evaluates the potential use of ultrasound irradiation to synthesize decyl oleate using Fermase CALBTM10000 under the solvent-free system (SFS). The optimal condition to achieve a maximum yield of 97.14% was found to be 1:2 oleic acid:decanol ratio, 1.8% (w/w) enzyme loading, 45°C temperature, 200 rpm agitation speed, 50 W power input, 50% duty cycle, 22 kHz frequency and reaction time of 25 minutes. The thermodynamic study was done to determine the change in entropy, Gibb's free energy, and change in enthalpy at various temperatures. The experimental results and kinetic study showed that the reaction followed ordered bi-bi model with kinetic parameters as rate of reaction (V max ) = 35.02 M/min/g catalyst, Michaelis constant for acid (K A ) = 34.47 M, Michaelis constant for alcohol (K B ) = 3.31 M, Inhibition constant (Ki) = 4542.4 M and sum of square error (SSE) = 0.000334. The application of ultrasound irradiation combined with biocatalyst and the absence of solvent intensified the process compared to the traditional stirring method using hexane as solvent.
Asunto(s)
Biocatálisis , Enzimas Inmovilizadas/química , Lipasa/química , Ácido Oléico/síntesis química , Ondas Ultrasónicas , Fenómenos Químicos , Cosméticos , Ácidos Decanoicos/química , Esterificación , Ésteres , Hexanos , Cinética , Lubricantes , Ácido Oléico/química , Solventes , Temperatura , TermodinámicaRESUMEN
In this study two different strategy were followed to obtain a D-fructose-oleic acid ester. One of the strategies has been well established enzymatic synthesis of an ester bond. The other strategy excluded the biocatalyst and only used a mixture of two organic solvents as the reaction media, 2-methyl-2-butanol / dimethyl sulfoxide or tert-butanol / dimethyl sulfoxide for the production of D-fructose-oleic acid ester. Ester products obtained were characterised by using FT-IR, NMR, by MS. Product yield was also assessed by HPLC. Results of structural analyses and yield measurement indicated that two approaches produced almost identical ester products.
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Dimetilsulfóxido/química , Ésteres/síntesis química , Fructosa/síntesis química , Ácido Oléico/síntesis química , Pentanoles/química , Alcohol terc-Butílico/química , Animales , Biocatálisis , Células Cultivadas , Cromatografía Líquida de Alta Presión , Esterificación , Ésteres/química , Ésteres/toxicidad , Fructosa/química , Fructosa/toxicidad , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Ácido Oléico/química , Ácido Oléico/toxicidad , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
Esterification of D-glucose with oleic- and palmitic acids were carried out in the absence and presence of a biocatalyst, Candida antarctica lipase. The reaction medium was a mixture of dimethyl sulphoxide and tert-butanol (1:4, v/v). The reaction products were analysed by FTIR, 1H-NMR and 13C-NMR, HSQC, and by ESI-MS. Results indicated that the ester products formed were 6-O-glucose oleate and 6-O-glucose palmitate both in the absence and in the presence of the biocatalyst, with yields above 90%.
Asunto(s)
Biocatálisis , Ésteres/síntesis química , Glucosa/química , Ácido Oléico/síntesis química , Ácidos Oléicos/química , Palmitatos/síntesis química , Ácidos Palmíticos/química , Alcohol terc-Butílico/química , Dimetilsulfóxido/química , Esterificación , Proteínas Fúngicas/química , Lipasa/químicaRESUMEN
Inefficient tumor accumulation and controlling drug release at the tumor site are two major obstacles limiting the antitumor efficacy of nanoparticle delivery systems. Inspired by the biological structure and function of low-density lipoprotein (LDL), a pH-sensitive ApoB-100/Oleic acid-DOX/NLC (AODN) nanoparticle based on nanostructured lipid carrier (NLC) was prepared in this study. The biological composition of ApoB-containing NLC nanoparticles is similar to that of LDL, which can effectively increase the cycle time and targeting efficiency of nanoparticles. Meantime, the doxorubicin prodrug strategy was used to increase the drug loading of the nanoparticles and achieve drug-sensitive release. In vitro results indicated that AODN nanoparticles can cause more drugs to be phagocytosed by LDL receptor-mediated endocytosis, thus showing high cytotoxicity in 4T1 cells. In vivo experiments have shown that pH-sensitive AODN nanoparticles can cause more drugs to accumulate in the tumor site, reducing systemic toxicity and effectively inhibiting orthotopic breast cancer. These data provide strong evidence that the strategy of combining bionics and prodrug technology provides a new approach to improving the efficiency of chemotherapy drugs in cancer treatment. STATEMENT OF SIGNIFICANCE: Inefficient tumor accumulation and controlling drug release at the tumor site are two major obstacles limiting the antitumor efficacy of nanoparticle delivery systems. Inspired by low density lipoprotein, a pH-sensitive ApoB-100/oleic acid-DOX/NLC (AODN) nanoparticle based on nanostructured lipid carrier (NLC) was prepared. Its biological composition is similar to that of LDL, which can effectively increase the cycle time and targeting efficiency of drugs. Then, the doxorubicin prodrug strategy was used to increase the drug loading of the nanoparticles and achieve drug-sensitive release. AODN nanoparticles can effectively inhibit tumor by effectively accumulating at tumor site and controlling release. The strategy of combining bionics and prodrug technology provides a new approach to improving the efficiency of chemotherapy drugs in cancer treatment.
Asunto(s)
Doxorrubicina/uso terapéutico , Lípidos/química , Lipoproteínas LDL/química , Nanopartículas/química , Neoplasias/tratamiento farmacológico , Profármacos/uso terapéutico , Animales , Apolipoproteínas B/metabolismo , Peso Corporal , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Doxorrubicina/química , Doxorrubicina/farmacología , Liberación de Fármacos , Femenino , Humanos , Concentración de Iones de Hidrógeno , Ratones Endogámicos BALB C , Ácido Oléico/síntesis química , Ácido Oléico/química , Profármacos/farmacología , Distribución Tisular , Resultado del Tratamiento , Carga TumoralRESUMEN
PURPOSE: This work aims to create a novel Cu2+ liposome with excellent loading stability and develop synergistic effect with disulfiram (DSF) for the treatment of tumor. METHODS: Copper oleate was incorporated into the liposome membrane via alcohol injection method in this work. In vitro release test was applied to evaluate the release profile of the liposomes. Pharmacokinetic studies were performed in rats and the antitumor efficacy was assessed in mice bearing hepatoma xenografts. RESULTS: The copper oleate liposome (Cu(OI)2-L) was formulated and the loading efficiency were more than 85%. TEM images confirmed that the Cu(OI)2-L had a spherical morphology with an average diameter of 100 nm. Cu(OI)2-L displayed a biphasic release profile, with >70% retained drug over 8 h incubation in PBS at pH 7.4. Pharmacokinetic studies demonstrated that Cu(OI)2-L had a prolonged circulation time and increased AUC when compared to the injection of copper oleate solution. The antitumor efficacy test demonstrated an enhanced tumor inhibition rate with the treatment of Cu(OI)2-L and DSF nanoparticles, indicating an improved synergistic antitumor effect. CONCLUSIONS: The Cu(OI)2-L was suitable to be employed in combination with disulfiram for tumor treatment and can also open up opportunities for targeted delivery of copper.
Asunto(s)
Antineoplásicos/síntesis química , Protocolos de Quimioterapia Combinada Antineoplásica/síntesis química , Cobre/química , Disulfiram/síntesis química , Neoplasias Hepáticas Experimentales/tratamiento farmacológico , Ácido Oléico/síntesis química , Animales , Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carcinoma de Ehrlich/tratamiento farmacológico , Carcinoma de Ehrlich/patología , Cobre/administración & dosificación , Disulfiram/administración & dosificación , Sinergismo Farmacológico , Neoplasias Hepáticas Experimentales/patología , Masculino , Ratones , Ácido Oléico/administración & dosificación , Polietilenglicoles/administración & dosificación , Polietilenglicoles/síntesis química , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Resultado del Tratamiento , Carga Tumoral/efectos de los fármacos , Carga Tumoral/fisiología , Ensayos Antitumor por Modelo de Xenoinjerto/métodosRESUMEN
Cationic lipo-oligomers containing unsaturated oleic acid are potent siRNA carriers based on electrostatic and hydrophobic lipo-polyplex formation and endosomal membrane destabilization. Lipo-oligomers can be produced by solid-phase-supported synthesis in sequence-defined form. However, the trifluoroacetic acid (TFA)-mediated removal of acid-labile protecting groups and cleavage from the resin can be accompanied by side products caused by the addition of TFA to the double bonds of oleic acid. Under aqueous conditions, these TFA adducts of oleic acid are converted into hydroxystearic acid derivatives. The cleavage protocol was optimized to decrease TFA adducts. The pure oleic acid (C18:1) containing lipo-oligomer was compared with analogous structures containing saturated or modified hydrophobic moieties (stearic acid (C18:0), hydroxystearic acid, and 8-nonanamidooctanoic acid). The structure containing intact oleic acid shows favorable pH dependency of lytic activity, efficient gene silencing, and excellent cell tolerability relative to its counterparts.
Asunto(s)
Ácido Oléico/síntesis química , ARN Interferente Pequeño/administración & dosificación , Técnicas de Síntesis en Fase Sólida/métodos , Animales , Línea Celular Tumoral , Genes Reporteros , Hemólisis , Humanos , Ratones , Ácido Oléico/química , Interferencia de ARN , ARN Interferente Pequeño/genética , Transfección/métodos , Ácido Trifluoroacético/síntesis química , Ácido Trifluoroacético/químicaRESUMEN
Lipases from Thermomyces lanuginosus (TLL) and Pseudomonas fluorescens (PFL) wereimmobilized on functionalized silica particles aiming their use in the synthesis of fructose oleate in a tert-butyl alcohol/water system. Silica particles were chemically modified with octyl (OS), octyl plus glutaraldehyde (OSGlu), octyl plus glyoxyl(OSGlx), and octyl plus epoxy groups(OSEpx). PFL was hyperactivated on all functionalized supports (more than 100% recovered activity) using low protein loading (1 mg/g), however, for TLL, this phenomenon was observed only using octyl-silica (OS). All prepared biocatalysts exhibited high stability by incubating in tert-butyl alcohol (half-lives around 50 h at 65 °C). The biocatalysts prepared using OS and OSGlu as supports showed excellent performance in the synthesis of fructose oleate. High estersynthesis was observed when a small amount of water (1%, v/v) was added to the organic phase, allowing an ester productivity until five times (0.88-0.96 g/L.h) higher than in the absence of water (0.18-0.34 g/L.h) under fixed enzyme concentration (0.51 IU/g of solvent). Maximum ester productivity (16.1-18.1 g/L.h) was achieved for 30 min of reaction catalyzed by immobilized lipases on OS and OSGlu at 8.4 IU/mL of solvent. Operational stability tests showed satisfactory stability after four consecutive cycles of reaction.
Asunto(s)
Enzimas Inmovilizadas , Fructosa/química , Lipasa/metabolismo , Ácido Oléico/síntesis química , Dióxido de Silicio , Biocatálisis , Estabilidad de Enzimas , Lipasa/química , Modelos Moleculares , Conformación Molecular , Solventes , AguaRESUMEN
Large zeolite crystals of ferrierite have been used to study the deactivation, at the single particle level, of the alkyl isomerisation catalysis of oleic acid and elaidic acid by a combination of visible micro-spectroscopy and fluorescence microscopy (both polarised wide-field and confocal modes). The large crystals did show the desired activity, albeit only traces of the isomerisation product were obtained and low conversions were achieved compared to commercial ferrierite powders. This limited activity is in line with their lower external non-basal surface area, supporting the hypothesis of pore mouth catalysis. Further evidence for the latter comes from visible micro-spectroscopy, which shows that the accumulation of aromatic species is limited to the crystal edges, while fluorescence microscopy strongly suggests the presence of polyenylic carbocations. Light polarisation associated with the spatial resolution of fluorescence microscopy reveals that these carbonaceous deposits are aligned only in the larger 10-MR channels of ferrierite at all crystal edges. The reaction is hence further limited to these specific pore mouths.
Asunto(s)
Boca/química , Ácido Oléico/química , Zeolitas/química , Catálisis , Isomerismo , Microscopía Fluorescente , Ácido Oléico/síntesis químicaRESUMEN
INTRODUCTION: Imaging fatty acid uptake and utilization has broad impact in investigating myocardial diseases, hepatic functions, tumor progression, and the metabolic state of adipose tissue. The SPECT tracer (123)I-15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) is a clinically used nuclear medicine tracer to image myocardial uptake of fatty acid. Although ((18)F-5) has been in clinical use for PET imaging of adipose tissue as well as the myocardium, here we developed a click oleate analog to compare to FTO, with the goal of improved stability to defluorination and suitability for imaging myocardial uptake and oxidation of fatty acids. METHODS: A rapid and convenient synthetic approach for a precursor to a (18)F-labeled oleate analog using click chemistry was developed and evaluated for PET imaging in fasted mice. RESULTS: The overall yield for the preparation of the labeling precursor of the clicked oleate analog was 12%. This precursor was efficiently radiolabeled with F-18 in 17% non-decay-corrected radiochemical yield. PET/CT imaging and biodistribution results show that this fatty acid analog had reasonable heart uptake (0.94±0.28 %ID/g at 0.5 h p.i.) and heart-to-muscle ratio (2.05±0.39 at 0.5h p.i.) and is a potential lead for developing new PET tracers to image fatty acid uptake and utilization using click chemistry methodologies. The synthetic route to FTO was optimized to three steps from known starting materials. CONCLUSION: While the uptake of the clicked oleic acid analog was sufficient for visualizing the myocardium in mice, the preliminary metabolism data suggest that only a fraction of the uptake was due to fatty acid beta-oxidation. Studies are under way to explore the uptake/oxidation mechanism and kinetics.
Asunto(s)
Ácidos Grasos/metabolismo , Radioisótopos de Flúor , Ácido Oléico/síntesis química , Tomografía de Emisión de Positrones/métodos , Animales , Transporte Biológico , Técnicas de Química Sintética , Marcaje Isotópico , Masculino , Ratones , Ácido Oléico/química , Ácido Oléico/farmacocinética , Distribución Tisular , Tomografía Computarizada por Rayos XRESUMEN
The current paper exemplifies the application of ultrasound technology to enzymatic synthesis of a cosmetic emollient ester, cetyl oleate. Fermase CALB™10000, a commercial Candida antarctica lipase B was used as a catalyst to accomplish the ultrasound supported synthesis. Multiple process parameters like reaction time, temperature, enzyme dose, alcohol to acid molar ratio, ultrasound power, frequency and speed of agitation were optimised. Maximum conversion of â¼95.96% was discerned at optimum conditions, i.e., 60°C temperature, 5% enzyme dose, 2:1 alcohol:acid ratio, 60 W ultrasound power, 25 kHz ultrasound frequency, 80% duty cycle and 80 rpm speed of agitation after purification steps. It was observed that the reaction reached equilibrium in a short duration of 30 min under the optimised conditions. This was considerably lesser than the time required for attaining equilibrium in conventional mechanical stirring method which was over 2h. Bisubstrate kinetic models like random bi-bi, ping pong bi-bi and ordered bi-bi were applied to the experimental data to determine initial rates and other kinetic parameters. Ordered bi-bi model showed the best fit with kinetic parameters, Vmax=0.029 M/min/gcatalyst, KA=0.00001 M, KB=4.8002 M, KiA=0.00014 M, KiB=3.7914 M & SSE=0.00022 for enzymatic cetyl oleate synthesis under ultrasound irradiation with inhibition by both acid and alcohol at high concentrations.
Asunto(s)
Biocatálisis , Técnicas de Química Sintética/métodos , Proteínas Fúngicas/metabolismo , Lipasa/metabolismo , Ácido Oléico/síntesis química , Sonicación/métodos , Enzimas Inmovilizadas/química , Enzimas Inmovilizadas/metabolismo , Proteínas Fúngicas/química , Cinética , Lipasa/química , Modelos Químicos , Ácido Oléico/química , TemperaturaRESUMEN
In order to obtain phosphatidylcholine (PC) with higher amount of oleic acid, the interesterification between soybean PC and Camellia oleifera oil (COO) rich in oleic acid catalyzed by lipase was studied in hexane. For this aim three commercially available immobilized lipases (Novozym 435, Lipozyme TLIM and Lipozyme RMIM) were assayed and Novozym 435 was finally selected for further optimization. The effects of the factors, such as PC concentration, substrate ratio, water amount, lipase dosage and temperature, on the oleic acid content in PC and PC recovery during the interesterification were investigated. The conditions of the interesterification were optimized using response surface methodology. The optimum conditions were as follows: lipase dosage 13 % (based on the mass of PC and COO), reaction temperature 55°C, water amount 5% (based on the mass of PC), reaction time 8 h, PC concentration 0.3g/mL (PC/hexane), PC-to-COO ratio 1:3 (acyl groups in PC/acyl groups in COO, mol/mol). Under these conditions, oleic acid content and PC recovery were 40.8 ± 0.5% and 69.0 ± 2.8%, respectively. Analysis of variance (ANOVA) showed that the regression models were adequate for predicting the interesterifiction. The orders of reaction variables affecting on oleic acid content and PC recovery were water amount > reaction time > lipase dosage > reaction temperature, and water amount > reaction temperature > lipase dosage > reaction time, respectively.
Asunto(s)
Bioquímica/métodos , Lipasa/química , Ácido Oléico/análisis , Ácido Oléico/síntesis química , Fosfatidilcolinas/química , Fosfatidilcolinas/síntesis química , Aceites de Plantas/química , Camellia/química , Catálisis , Enzimas Inmovilizadas , Esterificación , Proteínas Fúngicas , Organofosfatos , Glycine max/química , Temperatura , AguaRESUMEN
Multifunctional nanoprobes open exciting possibilities for accurate diagnosis and therapy. In this research, we developed a (64)Cu-labeled GdVO4:4%Eu two-dimension (2D) tetragonal ultrathin nanosheets (NSs) that simultaneously possess radioactivity, fluorescence, and paramagnetic properties for multimodal imaging. The carboxyl-functionalized Eu(3+)-doped GdVO4 NSs were synthesized by a facile solvothermal reaction, followed by ligand exchange with polyacrylic acid (PAA). With ultrathin thickness of â¼5 nm and width of â¼150 nm, the carboxyl-functionalized NSs were further modified by DOTA chelator for (64)Cu labeling and Asp-Gly-Glu-Ala (DGEA) peptide for integrin α2ß1 targeting. After initial evaluation of the cytotoxicity and targeting capability with PC-3 cells, the obtained multifunctional nanoprobes ((64)Cu-DOTA-GdVO4:4%Eu-DGEA) were further explored for targeted positron emission tomography (PET) and T1-weighted magnetic resonance imaging (MRI) of PC-3 tumor (prostate cancer, high integrin α2ß1 expression) in vivo. Based on the strong fluorescence of the NSs, the particle distribution in mouse tissues was also determined by fluorescent microscopy. In summary, GdVO4:4%Eu NS is a potential multimodal multiscale nanoprobe that could not only be used for in vivo imaging, but also be tracked in cellular scale and ex vivo due to its fluorescent property.
Asunto(s)
Europio , Gadolinio , Integrina alfa2beta1/química , Integrina alfa2beta1/metabolismo , Imagen por Resonancia Magnética , Imagen Multimodal , Nanopartículas , Tomografía de Emisión de Positrones , Vanadatos , Animales , Muerte Celular , Línea Celular Tumoral , Supervivencia Celular , Compuestos Heterocíclicos con 1 Anillo/síntesis química , Compuestos Heterocíclicos con 1 Anillo/química , Humanos , Masculino , Ratones Desnudos , Nanopartículas/ultraestructura , Ácido Oléico/síntesis química , Ácido Oléico/química , Oligopéptidos/síntesis química , Oligopéptidos/química , Espectrometría de Fluorescencia , Espectroscopía Infrarroja por Transformada de Fourier , Distribución Tisular , Difracción de Rayos X , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Oleic acid and its phospholipid derivatives are fundamental to the structure and function of cellular membranes. As a result, there has been increasing interest in the availability of their deuterated forms for many nuclear magnetic resonance, infrared, mass spectroscopy and neutron scattering studies. Here, we present for the first time a straightforward, large-scale (gram quantities) synthesis of highly deuterated [D32 ]oleic acid by using multiple, yet simple and high yielding reactions. The precursors for the synthesis of [D32 ]oleic acid are [D14 ]azelaic acid and [D17 ]nonanoic acid, which were obtained by complete deuteration (>98% D) of their (1) H forms by using metal catalysed hydrothermal H/D exchange reactions. The oleic acid was produced with ca. 94% D isotopic purity and with no contamination by the trans-isomer (elaidic acid). The subsequent synthesis of [D64 ]dioleoyl-sn-glycero-3-phosphocholine from [D32 ]oleic acid is also described.
Asunto(s)
Deuterio/química , Glicerilfosforilcolina/análogos & derivados , Ácido Oléico/química , Ácido Oléico/síntesis química , Técnicas de Química Sintética , Ácidos Dicarboxílicos/química , Ácidos Grasos/química , Glicerilfosforilcolina/síntesis química , Glicerilfosforilcolina/química , Metilación , FosfatidilcolinasRESUMEN
A series of oleic acid (OA) analogs containing terminal perfluoroalkyl groups (CF3, C2F5, n-C3F7, n-C4F9 or n-C8F17) was synthesized to clarify how the fluorinated chain length affects the stability and molecular packing of liquid-expanded OA monolayers at the air-water interface. Although the substitution of terminal CF3 group for CH3 in OA had no effect on monolayer stability, further fluorination led to a gradual increase in monolayer stability at 25 °C. Surface pressure-area isotherm revealed that partially fluorinated OA analogs form more expanded monolayers than OA at low surface pressures, and that the monolayer behavior of OA analogs with the even-carbon numbered fluorinated chain is almost the same as that of OA upon monolayer compression, whereas the behavior of OA analogs with the odd-carbon numbered fluorinated chain significantly differs from that of OA. These results indicate: (i) the terminal short part (at least C2 residue) in OA predominantly determines the liquid-expanded monolayer stability; (ii) the molecular packing state of OA may be perturbed by the substitution of a short odd-carbon numbered fluorinated chain; (iii) hence, OA analogs with even-carbon numbered chain are considered to be preferable as hydrophobic building blocks for the synthesis of fluorinated phospholipids.
Asunto(s)
Aire , Ácido Oléico/química , Agua/química , Halogenación , Concentración de Iones de Hidrógeno , Ácido Oléico/síntesis química , Propiedades de Superficie , TemperaturaRESUMEN
This study focuses on Candida rugosa lipase (CRL) immobilization by covalent attachment on poly(ethylene terephthalate)-grafted glycidyl methacrylate (PET-g-GMA) fiber. The immobilization yielded a protein loading of 2.38 mg g(-1) of PET-g-GMA fiber. The performances of the immobilized and free CRLs were evaluated with regard to hydrolysis of olive oil and esterification of oleic acid. The optimum activity pH of the CRL was changed by immobilization to neutral range. The maximum activity of the free and immobilized CRLs occurred at 40 and 45 °C respectively. The immobilized lipase retained 65% of its original activity at 50 °C for 2 h. It was found that the immobilized lipase stored at 4 °C retained 90% of its original activity after 35 days, whereas the free lipase stored at 4 °C retained 69% of its original activity after the same period. In the esterification experiments, the immobilized CRL could maintain a high activity at a water content range from 1.5 to 6% (v/v), while the activity of free CRL showed a clear dependence on water content and decreased rapidly at above 3% (v/v) water content. In addition, after five reuses, the esterification percent yield of the immobilized CRL slightly decreased from 29 to 27%.
Asunto(s)
Candida/enzimología , Enzimas Inmovilizadas/química , Glutaral/química , Interacciones Hidrofóbicas e Hidrofílicas , Lipasa/química , Ácido Oléico/química , Ácido Oléico/síntesis química , Alcoholes/química , Biocatálisis , Técnicas de Química Sintética , Estabilidad de Enzimas , Enzimas Inmovilizadas/metabolismo , Esterificación , Ésteres , Concentración de Iones de Hidrógeno , Hidrólisis , Cinética , Lipasa/metabolismo , Aceite de Oliva , Aceites de Plantas/química , Tereftalatos Polietilenos/química , Solventes/química , Temperatura , Agua/químicaRESUMEN
Multifunctional colloidal nanoparticles which exhibit fluorescence, superparamagnetism, and thermosensitivity are produced by two step seed emulsifier-free emulsion polymerization in the presence of oleic acid (OA) and sodium undecylenate (NaUA) modified Fe(3)O(4) nanoparticles. In the first step, St and NIPAM polymerize the NaUA on the surface of Fe(3)O(4) nanoparticles to form Fe(3)O(4)/poly(St-NIPAM) nanoparticles which act as seeds for the polymerization of Eu(AA)(3)Phen with the remaining St and NIPAM in the second step to form an outer fluorescent layer. The core-shell composite nanoparticles show reversible dimensional changes in response to external temperature stimuli. Fluorescence spectra acquired from the composites exhibit characteristic emission peaks of Eu(3+) at 594 and 619 nm and vivid red luminescence can be observed by 2-photon confocal scanning laser microscopy (CLSM). In vitro cytotoxicity tests based on the MTT assay demonstrate good cytocompatibility and the composites also possess paramagnetic properties with a maximum saturation magnetization of 6.45 emu/g and high transverse relaxivity rates (r(2)) of 411.78 mM(-1) s(-1). In vivo magnetic resonance imaging (MRI) studies show significant liver and spleen contrast with relative signal intensity reduction of about 86% 10 min after intravenous injection of the composites. These intriguing properties suggest that these nanocarriers have large clinical potential as multimodal optical/MRI probes.
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Compuestos Férricos/química , Imagen por Resonancia Magnética/métodos , Metales de Tierras Raras/química , Nanopartículas/química , Animales , Línea Celular , Emulsiones/metabolismo , Compuestos Férricos/análisis , Luminiscencia , Metales de Tierras Raras/análisis , Ácido Oléico/síntesis química , Polimerizacion , Ratas , Ratas Sprague-Dawley , TemperaturaRESUMEN
The use of human pluripotent stem cells (hPSCs) in cell therapy is hindered by the tumorigenic risk from residual undifferentiated cells. Here we performed a high-throughput screen of over 52,000 small molecules and identified 15 pluripotent cell-specific inhibitors (PluriSIns), nine of which share a common structural moiety. The PluriSIns selectively eliminated hPSCs while sparing a large array of progenitor and differentiated cells. Cellular and molecular analyses demonstrated that the most selective compound, PluriSIn #1, induces ER stress, protein synthesis attenuation, and apoptosis in hPSCs. Close examination identified this molecule as an inhibitor of stearoyl-coA desaturase (SCD1), the key enzyme in oleic acid biosynthesis, revealing a unique role for lipid metabolism in hPSCs. PluriSIn #1 was also cytotoxic to mouse blastocysts, indicating that the dependence on oleate is inherent to the pluripotent state. Finally, application of PluriSIn #1 prevented teratoma formation from tumorigenic undifferentiated cells. These findings should increase the safety of hPSC-based treatments.
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Inhibidores Enzimáticos/farmacología , Ácido Oléico/síntesis química , Células Madre Pluripotentes/efectos de los fármacos , Estearoil-CoA Desaturasa/antagonistas & inhibidores , Animales , Blastocisto/citología , Blastocisto/efectos de los fármacos , Blastocisto/metabolismo , Células Cultivadas , Humanos , Ratones , Células Madre Pluripotentes/citología , Células Madre Pluripotentes/metabolismoRESUMEN
In this paper, well-defined and regular-shaped Na3ScF6 nanocrystals (NCs) have been synthesized in high boiling organic solvents 1-octadecene (ODE) and oleic acid (OA), via the thermal decomposition of rare-earth oleate precursors. It is found that highly uniform monoclinic Na3ScF6 NCs with narrow size distribution have been obtained, which can easily be dispersed in cyclohexane solvent to form transparent colloid solutions. Upon 980 laser diode (LD) excitation, the relative up-conversion (UC) emission intensities of different colors in Yb(3+)/Er(3+), Yb(3+)/Tm(3+) and Yb(3+)/Ho(3+) doped Na3ScF6 can be tuned by altering the Yb(3+) doping concentration, resulting in the tunable multicolor in a wide range. On the basis of the emission spectra and the plot of luminescence intensity to pump power, the UC mechanisms of the co-doped Na3ScF6 NCs were investigated in detail. Moreover, the UC emission intensities can be significantly improved by coating a layer of Na3ScF6:Yb(3+)/Ln(3+) shell on Na3ScF6:Yb(3+)/Ln(3+) cores with respect to that of pure Na3ScF6:Yb(3+)/Ln(3+) core NCs. Furthermore, transparent and UC luminescent NCs/polydimethylsiloxane (PDMS) composites with regular dimensions were also fabricated by an in situ polymerization route. Uniform NCs with a wide variation of luminescence colors will show potential applications in diverse fields.
Asunto(s)
Elementos de la Serie de los Lantanoides/química , Sustancias Luminiscentes/química , Nanopartículas/química , Escandio/química , Fluoruro de Sodio/química , Alquenos/química , Elementos de la Serie de los Lantanoides/síntesis química , Luminiscencia , Sustancias Luminiscentes/síntesis química , Modelos Moleculares , Nanopartículas/ultraestructura , Ácido Oléico/síntesis química , Ácido Oléico/química , Transición de Fase , Fluoruro de Sodio/síntesis química , SolventesRESUMEN
Petroleum-collecting and dispersing complexes were synthesized on the basis of oleic acid and nitrogen-containing compounds. Surface-active properties (interfacial tension) of the obtained complexes were investigated by stalagmometric method. Petroleum-collecting and dispersing properties of the oleic acid complexes in diluted (5% wt. water or alcoholic solution) and undiluted form have been studied in waters of varying salinity (distilled, fresh and sea waters). Some of physico-chemical indices of the prepared compounds such as solubility, acid and amine numbers as well as electrical conductivity have been determined. The ability of oleic acid complex with ethylenediamine as petro-collecting and dispersing agent towards different types of petroleum has been studied. The influence of thickness and "age" of the petroleum slick on collecting and dispersing capacity of this complex has been clarified. Surface properties studied included critical micelle concentration (CMC), maximum surface excess (Γ(max)), and minimum surface area (A(min)). Free energies of micellization (ΔG°(mic)) and adsorption (ΔG°(ads)) were calculated.
Asunto(s)
Compuestos de Nitrógeno/química , Ácido Oléico/química , Contaminación por Petróleo/análisis , Petróleo/análisis , Tensoactivos/química , Contaminantes Químicos del Agua/aislamiento & purificación , Agua/química , Fenómenos Químicos , Ácido Oléico/síntesis química , Espectroscopía Infrarroja por Transformada de Fourier , Tensión Superficial , TermodinámicaRESUMEN
The present study enumerates the synthesis, spectroscopic characterization, and evaluation of anticancer potential of esters of two n-9 fatty acids viz., oleic acid (OLA) and ricinoleic acid (RCA) with 2,4- or 2,6-diisopropylphenol. The synthesis strategy involved esterification of the hydroxyl group of diisopropylphenol (propofol) to the terminal carboxyl group of n-9 fatty acid. The synthesized propofol-n-9 conjugates having greater lipophilic character were tested initially for cytotoxicity in-vitro. The conjugates showed specific growth inhibition of cancer cell lines whereas no effect was observed in normal cells. In general, pronounced growth inhibition was found against the human skin malignant melanoma cell line (SK-MEL-1). The anticancer potential was also determined by testing the effect of these conjugates on cell migration, cell adhesion and induction of apoptosis in SK-MEL-1 cancer cells. Propofol-OLA conjugates significantly induced apoptosis in contrast to propofol-RCA conjugates which showed only weak signals for cytochrome c. Conclusively, the synthesized novel ester conjugates showed considerable moderation of anti-tumor activity. This preliminary study places in-house synthesized conjugates into the new class of anticancer agents that possess selectivity toward cancer cells over normal cells.