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1.
ACS Appl Bio Mater ; 6(6): 2505-2513, 2023 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-37289471

RESUMO

X-ray-triggered scintillators (Sc) and photosensitizers (Ps) have been developed for X-ray-induced photodynamic therapy (X-PDT) to selectively destruct deep tissue tumors with a low X-ray dose. This study designed terbium (Tb)-rose bengal (RB) coordination nanocrystals (T-RBNs) by a solvothermal treatment, aiming to reduce photon energy dissipation between Tb3+ and RB and thus increase the reactive oxygen species (ROS) production efficiency. T-RBNs synthesized at a molar ratio of [RB]/[Tb] = 3 exhibited a size of 6.8 ± 1.2 nm with a crystalline property. Fourier transform infrared analyses of T-RBNs indicated successful coordination between RB and Tb3+. T-RBNs generated singlet oxygen (1O2) and hydroxyl radicals (•OH) under low-dose X-ray irradiation (0.5 Gy) via scintillating and radiosensitizing pathways. T-RBNs produced ∼8-fold higher ROS amounts than bare RB and ∼3.6-fold higher ROS amounts than inorganic nanoparticle-based controls. T-RBNs did not exhibit severe cytotoxicity up to 2 mg/mL concentration in cultured luciferase-expressing murine epithelial breast cancer (4T1-luc) cells. Furthermore, T-RBNs were efficiently internalized into cultured 4T1-luc cells and induced DNA double strand damage, as evidenced by an immunofluorescence staining assay with phosphorylated γ-H2AX. Ultimately, under 0.5 Gy X-ray irradiation, T-RBNs induced >70% 4T1-luc cell death via simultaneous apoptosis/necrosis pathways. Overall, T-RBNs provided a promising Sc/Ps platform under low-dose X-PDT for advanced cancer therapy.


Assuntos
Neoplasias da Mama , Nanopartículas , Fotoquimioterapia , Humanos , Animais , Camundongos , Feminino , Rosa Bengala/farmacologia , Rosa Bengala/química , Térbio/farmacologia , Térbio/química , Térbio/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Raios X , Nanopartículas/uso terapêutico , Nanopartículas/química
2.
Anal Bioanal Chem ; 415(2): 235-244, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36380245

RESUMO

Green coffee is coming into vogue as a food that contains remarkable contents of antioxidants like chlorogenic acid (ChA) and induces mild stimulation to the consumer. While most methods for determination of ChA require chromatographic separation prior its quantitation, we present the first probe and a simple, sensitive and validated luminescence method for the determination of chlorogenic acid in green and roasted coffee infusion samples that does not require a chromatographic separation. ChA can remarkably quench the luminescence intensity of the Tb3+ complex with 1-(furan-2-ylmethyl)-4-hydroxy-N-(4-methylpyridin-2-yl)-2-oxo-1,2,5,6,7,8-hexahydroquinoline-3-carboxamide (R3) in aqueous solution containing urotropine buffer at a near neutral pH 7.5 at λexc = 315 nm and λem = 545 nm. Under optimal conditions, the quenching of the luminescence intensity is directly proportional to the concentration of ChA in the range of 0.5-30 µg/mL, and the detection limit is 180 ng/mL. From measurements of luminescence decay time, it was determined that both static and dynamic quenching is induced upon coordination of ChA to Tb-R3. The related quenching constants are KS = 5.97∙104 M-1 and KD = 1.05⋅104 M-1. Finally, the method was applied successfully to the determination of ChA in real green and roasted coffee infusion samples and validated by HPLC to yield very closely matching concentrations of both methods. Therefore, this method can serve for a simple quality control of total ChA contents in coffee prior and after roasting.


Assuntos
Ácido Clorogênico , Café , Café/química , Ácido Clorogênico/análise , Térbio/química , Luminescência , Antioxidantes/farmacologia
3.
Luminescence ; 35(4): 594-600, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31912601

RESUMO

This paper focuses on an optical study of a Tb3+ /Bi3+ -doped and Sm3+ /La3+ - doped Ca2 Al2 SiO7 phosphor synthesized using combustion methods. Here, Ca2 Al2 SiO7 :Sm3+ showed a red emission band under visible light excitation but, when it co-doped with La3+ ions, the emission intensity was further enhanced. Ca2 Al2 SiO7 :Tb3+ shows the characteristic green emission band under near-ultraviolet light excitation wavelengths, co-doping with Bi3+ ions produced enhanced photoluminescence intensity with better colour tunable properties. The phosphor exhibited better phase purity and crystallinity, confirmed by X-ray diffraction. Binding energies of Ca(2p), Al(2p), Si(2p), O(1s) were studied using X-ray photoelectron spectroscopy. The reported phosphor may be a promising visible light excited red phosphor for light-emitting diodes and energy conversion devices.


Assuntos
Substâncias Luminescentes/química , Alumínio/química , Bismuto/química , Cálcio/química , Lantânio/química , Substâncias Luminescentes/síntese química , Medições Luminescentes , Fósforo/química , Espectroscopia Fotoeletrônica , Samário/química , Térbio/química
4.
Mater Sci Eng C Mater Biol Appl ; 102: 810-819, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31147053

RESUMO

The significance of Tb3+ inclusions at the zirconia toughened alumina (ZTA) structure was explored. The influence of Tb3+ content at the crystal structures of ZrO2 and Al2O3 and the resultant optical, mechanical, magnetic and cytotoxicity properties were deliberated. The critical role of Tb3+ to attain a structurally stable ZTA until 1500 °C is ensured. Depending on the Tb3+ content, either tetragonal zirconia (t-ZrO2) or cubic zirconia (c-ZrO2) structures were stabilized while the propensity of Tb3+ reaction with Al2O3 to yield TbAlO3 is transpired only after exceeding the occupancy limit in ZrO2. The green emission and paramagnetic features are imparted by the Tb3+ inclusions at the ZTA structure. Dense and pore free microstructures with a direct impact on the improved mechanical features of ZTA is empowered by the presence of Tb3+. Further, the results from MTT assay and live/dead cell staining ensured the negligence of Tb3+ contained ZTA systems to induce toxicity.


Assuntos
Óxido de Alumínio/química , Luminescência , Térbio/química , Zircônio/química , Linhagem Celular Tumoral , Humanos , Fenômenos Magnéticos , Análise Espectral Raman , Propriedades de Superfície , Temperatura , Difração de Raios X
5.
Molecules ; 24(4)2019 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-30791537

RESUMO

(Gd0.93-xTb0.07Eux)2O3 (x = 0⁻0.10) phosphors shows great potential for applications in the lighting and display areas. (Gd0.93-xTb0.07Eux)2O3 phosphors with controlled morphology were prepared by a hydrothermal method, followed by calcination at 1100 °C. XRD, FE-SEM, PL/PLE, luminescent decay analysis and thermal stability have been performed to investigate the Eu3+ content and the effects of hydrothermal conditions on the phase variation, microstructure, luminescent properties and energy transfer. Optimum excitation wavelength at ~308 nm nanometer ascribed to the 4f8-4f75d¹ transition of Tb3+, the (Gd0.93-xTb0.07Eux)2O3 phosphors display both Tb3+and Eu3+ emission with the strongest emission band at ~611 nm. For increasing Eu3+ content, the Eu3+ emission intensity increased as well while the Tb3+ emission intensity decreased owing to Tb3+→Eu3+ energy transfer. The energy transfer efficiencies were calculated and the energy transfer mechanism was discussed in detail. The lifetime for both the Eu3+ and Tb3+ emission decreases with the Eu3+ addition, the former is due to the formation of resonant energy transfer net, and the latter is because of contribution by Tb3+→Eu3+ energy transfer. The phosphor morphology can be controlled by adjusting the hydrothermal condition (reaction pH), and the morphological influence to the luminescent properties (PL/PLE, decay lifetime, etc.) has been studied in detail.


Assuntos
Európio/química , Metais Terras Raras/química , Óxidos/química , Fósforo/química , Térbio/química
6.
Anal Chem ; 91(4): 2595-2599, 2019 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-30712345

RESUMO

A novel 3D metal-organic framework (MOF){[Tb3(CBA)2(HCOO)(µ3-OH)4(H2O)]·2H2O·0.5DMF} n (S-1) was synthesized by the solvothermal method. The crystal structure indicates that [Tb4O4] cubane clusters self-assemble into an infinite chain by sharing vertex, which is further linked to adjacent chains through 1,1-cyclobutanedicarboxylic acid ligand (H2CBA), resulting in a honeycomb arrayed framework. S-1 possesses excellent water stability and still retains intact structure after exposure to water for 10 weeks or boiling water for 10 weeks. Interestingly, S-1 acts as a luminescence sensor to selectively and sensitively detect quercetin with the limit of detection (LOD) as low as 0.23 ppm (7.6 × 10-7 M). The relationship between relative luminescence intensity and concentration obeys linear in the range of 0-300 ppm (0-993 µM), which allows quantitative detection of quercetin. Importantly, S-1 can be reused at least six times with almost no change in luminescent intensity. Compared with the high performance liquid chromatography-mass spectrometry (HPLC-MS) method, S-1 was used to determine the content of quercetin in onionskin and apple peel samples with satisfactory results. Furthermore, a portable S-1 test paper is also developed and expected to be applied in practice. To our knowledge, S-1 is the first example of MOFs as luminescent sensor for quercetin.


Assuntos
Substâncias Luminescentes/química , Estruturas Metalorgânicas/química , Quercetina/análise , Reutilização de Equipamento , Limite de Detecção , Substâncias Luminescentes/síntese química , Medições Luminescentes/instrumentação , Medições Luminescentes/métodos , Malus/química , Estruturas Metalorgânicas/síntese química , Cebolas/química , Papel , Térbio/química
7.
J Inorg Biochem ; 193: 15-24, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30660047

RESUMO

N­(6­Aminohexyl)­5­chloro­1­naphthalenesulfonamide (W-7), a kind of adjuvant chemotherapy, can bind to calmodulin and inhibit Ca2+/calmodulin-regulated enzyme activities and cell proliferation. Similar to calmodulin, euplotes octocarinatus centrin (EoCen) belongs to EF-hand superfamily of calcium-binding proteins. It is associated with nucleotide excision repair (NER), cell division cycle and ciliogenesis. In the present study, the comparative interaction of W-7 with EoCen was first examined by using various spectroscopic, calorimetric methods and molecular docking. The obtain results recommend that only one W-7 molecule is identified binding to the C-terminal hydrophobic pocket of centrin that normally plays a role in anchoring targets. Methyl groups of Ala126, Met141, Ile161 and M162 of C-terminal may react with W-7 chloronaphthalene ring, other aliphatic or aromatic side-chains in a deep hydrophobic pocket of protein. Circular dichroism (CD) and fluorescence lifetime experiments reveal that W-7 triggers a conformational change of centrin. As a result, W-7 is identified to be an antagonist of centrin. It appears to inhibit the centrin-mediated activation of target proteins by blocking the hydrophobic pocket. Moreover, the complex formation leads to affinity decrease of Tb3+ binding to C-terminal of protein and self-assembly affected. Our present study provides the first view of centrin recognizing a naphthalene-sulfonamide derivative. It is proposed that W-7 and its analogues can serve as a useful tool for research on the participation of centrin in biological processes and cell biology-related studies.


Assuntos
Proteínas de Ligação ao Cálcio/metabolismo , Sulfonamidas/metabolismo , Térbio/metabolismo , Sítios de Ligação , Proteínas de Ligação ao Cálcio/antagonistas & inibidores , Proteínas de Ligação ao Cálcio/química , Euplotes/química , Simulação de Acoplamento Molecular , Ligação Proteica , Sulfonamidas/química , Térbio/química
8.
Luminescence ; 34(5): 460-464, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30652409

RESUMO

Consumption of herbal teas, infusions and other plant-related products has always been popular due to the related health benefits. However, the safety of these products needs to be assessed, for example monitoring the potential presence of contaminants such as pesticides. In this paper, we report an analytical method for determining three neonicotinoid insecticides - thiacloprid, thiamethoxam, and imidacloprid - that are widely used worldwide. This method is based on quenching by analytes of the luminescence signal of terbium ions. Terbium presents a time-resolved luminescence signal at 256/545 nm/nm, which is quenched by the presence of low concentrations of the selected analytes. Detection limits of 0.1, 0.2 or 0.75 µg ml-1 were obtained for thiamethoxam, thiacloprid and imidacloprid, respectively. Recovery experiments in different teas (green tea, black tea, chamomile, peppermint) were performed at concentrations lower than the maximum residue limits established by the European Union and the Codex Alimentarius for tea samples. In all cases, satisfactory recovery yields were observed, and the results were compared with a chromatographic reference method. The proposed method therefore proved suitable for quantifying these insecticides, fulfilling the current legislation.


Assuntos
Inseticidas/análise , Medições Luminescentes/métodos , Neonicotinoides/análise , Nitrocompostos/análise , Chá/química , Térbio/química , Tiametoxam/análise , Tiazinas/análise , Contaminação de Alimentos/análise , Luminescência , Sensibilidade e Especificidade
9.
Biomaterials ; 184: 31-40, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30195803

RESUMO

The limitation of light penetration depth invalidates the application of photodynamic therapy in deep-seated tumors. X-ray excited photodynamic therapy (X-PDT), which is based on X-rays excited luminescent nanoparticles (XLNP), provides a new strategy for PDT in deep tissues. However, the high X-ray dosage used and non-specific cytotoxicity of the nanoparticle-photosensitizer nanocomposite (NPs-PS) hamper in-vivo X-PDT applications. To address these problems, a simple and efficient NPs-PS nanocomposite using ß-NaGdF4: Tb3+ nanoparticles and widely used PS called Rose Bengal (RB) was designed. With perfectly matched spectrum of NPs emission and RB absorption upon X-ray excitation and covalent conjugation of a large amount of RB on NP surfaces to minimize the energy transfer distance, the system demonstrated ultra-high FRET efficiency up to 99.739%, which leads to maximum production of singlet oxygen for PDT with significantly increased anti-tumor efficacy. By 2-aminoethylphosphonic acid surface modification of NPs, excellent biocompatibility was achieved even at a high concentration of 1 mg/mL. The in-vivo X-PDT efficacy was found around 90% of HepG2 tumor growth inhibition with X-ray dose of only 1.5 Gy, which shows the best anti-tumor efficacy at same X-ray dose level reported so far. The present work provides a promising platform for in-vivo X-PDT in deep tumors.


Assuntos
Gadolínio/química , Nanocompostos/química , Fármacos Fotossensibilizantes/química , Rosa Bengala/química , Térbio/química , Animais , Sobrevivência Celular , Feminino , Transferência Ressonante de Energia de Fluorescência , Células Hep G2 , Humanos , Camundongos Endogâmicos BALB C , Fotoquimioterapia , Oxigênio Singlete/metabolismo , Raios X
10.
Spectrochim Acta A Mol Biomol Spectrosc ; 203: 461-471, 2018 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-29894961

RESUMO

In this study, a novel fluorescent probe, TbIII-dtpa-bis(2,6-diaminopurine) (Tb-dtpa-bdap), is designed based on the principle of complementary base pairing and synthesized for uric acid detection. The synthesized fluorescent probe is characterized by 1H NMR, 13C NMR, infra-red (IR) spectrum and ultraviolet-visible (UV-vis) spectra. It is found that the fluorescence of Tb-dtpa-bdap solution can be quenched obviously in the presence of uric acid. The affecting factors, including solution acidity, uric acid concentration and interfering substances, on the detection of uric acid using this probe are examined. Under optimized conditions, the fluorescence intensities of Tb-dtpa-bdap solution towards different uric acid concentrations show a linear response in the range from 1.00 × 10-5 mol·L-1 to 5.00 × 10-5 mol·L-1 with a linear correlation coefficient (R2) of 0.9877. And the obtained limit of detection (LOD) is about 5.80 × 10-6 mol·L-1, which is lower than the level of uric acid in actual urine. The mechanism on the detection of uric acid by using Tb-dtpa-bdap is inferred from the experimental results. The facts demonstrate that the proposed fluorescent probe can be successfully applied for the determination of uric acid in human urine samples.


Assuntos
2-Aminopurina/análogos & derivados , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Ácido Pentético/química , Térbio/química , Ácido Úrico/urina , 2-Aminopurina/química , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Humanos , Concentração de Íons de Hidrogênio , Espectroscopia de Prótons por Ressonância Magnética , Soluções , Espectrometria de Fluorescência , Espectroscopia de Infravermelho com Transformada de Fourier
11.
Talanta ; 186: 97-103, 2018 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-29784425

RESUMO

Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin produced by fungi on stored grains. The earlier detection methods used for ZEN rely on expensive equipment, time-consuming sample preparation and temperature sensitive antibodies. The current work, proposed a novel strategy based on ZEN aptamer labeled with amine-functionalized magnetic nanoparticle (MNPs) as a capture probe and time-resolved fluorescence (TRFL) nanoparticles labeled with complementary DNA (cDNA) as a signal probe. Under the optimized conditions, TRFL intensity at 544 nm was used to measure ZEN (R2 = 0.9920) in the range of 0.001-10 ng mL-1 and limits of detection (LOD) for proposed method was 0.21 pg mL-1. The specificity of bioassay was also determined by using other mycotoxins (OTA, AFB2, DON and Patulin) and results showed that the aptamer are specific to recognize only ZEN. The analytical applications of the present bioassay in maize and wheat samples were also examined and results were compared with existing methods. Based on these findings, it is suggested to use current rapid and simple bioassay for the determination of ZEN in food and agricultural products.


Assuntos
Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais , Corantes Fluorescentes/química , Contaminação de Alimentos/análise , Nanopartículas de Magnetita/química , Zearalenona/análise , Cério/química , Fluorescência , Corantes Fluorescentes/síntese química , Fluoretos/química , Nanopartículas/química , Tamanho da Partícula , Propriedades de Superfície , Térbio/química , Fatores de Tempo , Triticum/química , Ítrio/química , Zea mays/química
12.
J Am Chem Soc ; 137(7): 2484-94, 2015 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-25689372

RESUMO

Nonreceptor protein tyrosine kinases (NRTKs) are essential for cellular homeostasis and thus are a major focus of current drug discovery efforts. Peptide substrates that can enhance lanthanide ion luminescence upon tyrosine phosphorylation enable rapid, sensitive screening of kinase activity, however design of suitable substrates that can distinguish between tyrosine kinase families is a huge challenge. Despite their different substrate preferences, many NRTKs are structurally similar even between families. Furthermore, the development of lanthanide-based kinase assays is hampered by incomplete understanding of how to integrate sequence selectivity with metal ion binding, necessitating laborious iterative substrate optimization. We used curated proteomic data from endogenous kinase substrates and known Tb(3+)-binding sequences to build a generalizable in silico pipeline with tools to generate, screen, align, and select potential phosphorylation-dependent Tb(3+)-sensitizing substrates that are most likely to be kinase specific. We demonstrated the approach by developing several substrates that are selective within kinase families and amenable to high-throughput screening (HTS) applications. Overall, this strategy represents a pipeline for developing efficient and specific assays for virtually any tyrosine kinase that use HTS-compatible lanthanide-based detection. The tools provided in the pipeline also have the potential to be adapted to identify peptides for other purposes, including other enzyme assays or protein-binding ligands.


Assuntos
Ensaios Enzimáticos/métodos , Proteínas Tirosina Quinases/metabolismo , Térbio/química , Sequência de Aminoácidos , Técnicas Biossensoriais , Simulação por Computador , Avaliação Pré-Clínica de Medicamentos , Ensaios de Triagem em Larga Escala , Humanos , Células K562 , Medições Luminescentes , Dados de Sequência Molecular , Biblioteca de Peptídeos , Peptídeos/química , Peptídeos/farmacologia , Fosforilação , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Proteínas Tirosina Quinases/antagonistas & inibidores , Proteínas Tirosina Quinases/química , Bibliotecas de Moléculas Pequenas/farmacologia
13.
J Hazard Mater ; 272: 96-101, 2014 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-24681591

RESUMO

This paper is a comparative study of recycling rare earth elements from waste phosphor, which focuses on the leaching rate and the technical principle. The traditional and dual dissolution by hydrochloric acid (DHA) methods were compared. The method of dual dissolution by hydrochloric acid has been developed. The Red rare earth phosphor (Y0.95Eu0.05)2O3 in waste phosphor is dissolved during the first step of acid leaching, while the Green phosphor (Ce0.67Tb0.33MgAl11O19) and the Blue phosphor (Ba0.9Eu0.1MgAl10O17) mixed with caustic soda are obtained by alkali sintering. The excess caustic soda and NaAlO2 are removed by washing. The insoluble matter is leached by the hydrochloric acid, followed by solvent extraction and precipitation (the DHA method). In comparison, the total leaching rate of the rare earth elements was 94.6% by DHA, which is much higher than 42.08% achieved by the traditional method. The leaching rate of Y, Eu, Ce and Tb reached 94.6%, 99.05%, 71.45%, and 76.22%, respectively. DHA can decrease the consumption of chemicals and energy. The suggested DHA method is feasible for industrial applications.


Assuntos
Ácido Clorídrico/química , Metais Terras Raras/química , Fósforo/análise , Poluentes Químicos da Água/química , Ácidos , Cério/química , Európio/química , Filtração , Fósforo/química , Solubilidade , Solventes/química , Térbio/química , Difração de Raios X , Ítrio/química
14.
Biochemistry ; 52(47): 8510-7, 2013 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-24164461

RESUMO

Membrane fusion is broadly envisioned as a two- or three-step process proceeding from contacting bilayers through one or two semistable, nonlamellar lipidic intermediate structures to a fusion pore. A true fusion event requires mixing of contents between compartments and is monitored by the movement of soluble molecules between trapped compartments. We have used poly(ethylene glycol) (PEG) to rapidly generate an ensemble aggregated state A that proceeds sequentially through intermediates (I1 and/or I2) to a final fusion pore state (FP) with rate constants k1, k2, and k3. Movement of moderately sized solutes (e.g., Tb³âº/dipicolinic acid) has been used to detect pores assigned to intermediate states as well as to the final state (FP). Analysis of ensemble kinetic data has required that mixing of contents occurs with defined probabilities (αi) in each ensemble state, although it is unclear whether pores that form in different states are different. We introduce here a simple new assay that employs fluorescence resonance energy transfer (FRET) between a 6-carboxyfluorescein (donor) and tetramethylrhodamine (acceptor), which are covalently attached to complementary sequences of 10 bp oligonucleotides. Complementary sequences of fluorophore-labeled oligonucleotides were incorporated in vesicles separately, and the level of FRET increased in a simple exponential fashion during PEG-mediated fusion. The resulting rate constant corresponded closely to the slow rate constant of FP formation (k3) derived from small molecule assays. Additionally, the total extent of oligonucleotide mixing corresponded to the fraction of content mixing that occurred in state FP in the small molecule assay. The results show that both large "final pores" and small (presumably transient) pores can form between vesicles throughout the fusion process. The implications of this result for the mechanism of membrane fusion are discussed.


Assuntos
Estruturas da Membrana Celular/química , Fusão de Membrana , Fluoresceínas/química , Transferência Ressonante de Energia de Fluorescência , Corantes Fluorescentes/química , Indicadores e Reagentes/química , Cinética , Oligonucleotídeos/química , Fosfatidilcolinas/química , Fosfatidiletanolaminas/química , Ácidos Picolínicos/química , Polietilenoglicóis/química , Porosidade , Rodaminas/química , Solubilidade , Esfingomielinas/química , Propriedades de Superfície , Térbio/química
15.
J Nucl Med ; 53(12): 1951-9, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23139086

RESUMO

UNLABELLED: Terbium offers 4 clinically interesting radioisotopes with complementary physical decay characteristics: (149)Tb, (152)Tb, (155)Tb, and (161)Tb. The identical chemical characteristics of these radioisotopes allow the preparation of radiopharmaceuticals with identical pharmacokinetics useful for PET ((152)Tb) and SPECT diagnosis ((155)Tb) and for α- ((149)Tb) and ß(-)-particle ((161)Tb) therapy. The goal of this proof-of-concept study was to produce all 4 terbium radioisotopes and assess their diagnostic and therapeutic features in vivo when labeled with a folate-based targeting agent. METHODS: (161)Tb was produced by irradiation of (160)Gd targets with neutrons at Paul Scherrer Institute or Institut Laue-Langevin. After neutron capture, the short-lived (161)Gd decays to (161)Tb. (149)Tb, (152)Tb, and (155)Tb were produced by proton-induced spallation of tantalum targets, followed by an online isotope separation process at ISOLDE/CERN. The isotopes were purified by means of cation exchange chromatography. For the in vivo studies, we used the DOTA-folate conjugate cm09, which binds to folate receptor (FR)-positive KB tumor cells. Therapy experiments with (149)Tb-cm09 and (161)Tb-cm09 were performed in KB tumor-bearing nude mice. Diagnostic PET/CT ((152)Tb-cm09) and SPECT/CT ((155)Tb-cm09 and (161)Tb-cm09) studies were performed in the same tumor mouse model. RESULTS: Carrier-free terbium radioisotopes were obtained after purification, with activities ranging from approximately 6 MBq (for (149)Tb) to approximately 15 MBq (for (161)Tb). The radiolabeling of cm09 was achieved in a greater than 96% radiochemical yield for all terbium radioisotopes. Biodistribution studies showed high and specific uptake in FR-positive tumor xenografts (23.8% ± 2.5% at 4 h after injection, 22.0% ± 4.4% at 24 h after injection, and 18.4% ± 1.8% at 48 h after injection). Excellent tumor-to-background ratios at 24 h after injection (tumor to blood, ≈ 15; tumor to liver, ≈ 5.9; and tumor to kidney, ≈ 0.8) allowed the visualization of tumors in mice using PET ((152)Tb-cm09) and SPECT ((155)Tb-cm09 and (161)Tb-cm09). Compared with no therapy, α- ((149)Tb-cm09) and ß(-)-particle therapy ((161)Tb-cm09) resulted in a marked delay in tumor growth or even complete remission (33% for (149)Tb-cm09 and 80% for (161)Tb-cm09) and a significantly increased survival. CONCLUSION: For the first time, to our knowledge, 4 terbium radionuclides have been tested in parallel with tumor-bearing mice using an FR targeting agent. Along with excellent tumor visualization enabled by (152)Tb PET and (155)Tb SPECT, we demonstrated the therapeutic efficacy of the α-emitter (149)Tb and ß(-)-emitter (161)Tb.


Assuntos
Ácido Fólico/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Radioisótopos/uso terapêutico , Térbio/uso terapêutico , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Partículas alfa/uso terapêutico , Animais , Partículas beta/uso terapêutico , Feminino , Receptores de Folato com Âncoras de GPI/metabolismo , Ácido Fólico/química , Ácido Fólico/uso terapêutico , Compostos Heterocíclicos com 1 Anel/química , Humanos , Células KB , Camundongos
16.
J Phys Chem A ; 116(33): 8464-74, 2012 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-22835039

RESUMO

Lu(3)Al(5)O(12) (LuAG) doped with Ce(3+) is a promising scintillator material with a high density and a fast response time. The light output under X-ray or γ-ray excitation is, however, well below the theoretical limit. In this paper the influence of codoping with Tb(3+) is investigated with the aim to increase the light output. High resolution spectra of singly doped LuAG (with Ce(3+) or Tb(3+)) are reported and provide insight into the energy level structure of the two ions in LuAG. For Ce(3+) zero-phonon lines and vibronic structure are observed for the two lowest energy 5d bands and the Stokes' shift (2 350 cm(-1)) and Huang-Rhys coupling parameter (S = 9) have been determined. Tb(3+) 4f-5d transitions to the high spin (HS) and low spin (LS) states are observed (including a zero-phonon line and vibrational structure for the high spin state). The HS-LS splitting of 5400 cm(-1) is smaller than usually observed and is explained by a reduction of the 5d-4f exchange coupling parameter J by covalency. Upon replacing the smaller Lu(3+) ion with the larger Tb(3+) ion, the crystal field splitting for the lowest 5d states increases, causing the lowest 5d state to shift below the (5)D(4) state of Tb(3+) and allowing for efficient energy transfer from Tb(3+) to Ce(3+) down to the lowest temperatures. Luminescence decay measurements confirm efficient energy transfer from Tb(3+) to Ce(3+) and provide a qualitative understanding of the energy transfer process. Co-doping with Tb(3+) does not result in the desired increase in light output, and an explanation based on electron trapping in defects is discussed.


Assuntos
Óxido de Alumínio/química , Cério/química , Transferência de Energia , Luminescência , Lutécio/química , Térbio/química , Medições Luminescentes
17.
Opt Express ; 19 Suppl 1: A1-6, 2011 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-21263707

RESUMO

A class of thermal stable of green-emitting phosphors Ba(3)Y(PO(4))(3):Ce(3+),Tb(3+) (BYP:Ce(3+),Tb(3+)) and red-emitting phosphors Ca(3)Y(AlO)(3)(BO(3))(4):Eu(3+) (CYAB:Eu(3+)) for white-light fluorescent lamps were synthesized by high temperature solid-state reaction. We observed a decay of only 3% at 150 °C for BYP:0.25Ce3+,0.25Tb3+ (3% for LaPO4:Ce(3+),Tb(3+)), and a decay of 4% for CYAB:0.5Eu(3+) (7% for Y(2)O(3):Eu(3+), 24% for Y(2)O(2)S:Eu(3+)). The emission intensity of composition-optimized Ba(3)(Y(0.5)Ce(0.25)Tb(0.25))(PO(4))(3) is 70% of that of commercial LaPO(4):Ce(3+),Tb(3+) phosphors, and the CIE chromaticity coordinates are found to be (0.323, 0.534). The emission intensity of Ca(3)(Y(0.5)Eu(0.5))(AlO)(3)(BO(3))(4) is 70% and 83% of those of Y(2)O(3):Eu(3+) and Y(2)O(2)S:Eu(3+) phosphors, respectively, and the CIE chromaticity coordinates are redder (0.652, 0.342) than those of Y(2)O(3):Eu(3+) (0.645, 0.347) and Y(2)O(2)S:Eu(3+) (0.647, 0.343). A white-light fluorescent lamp is fabricated using composition-optimized Ba(3)(Y(0.5)Ce(0.25)Tb(0.25))(PO(4))(3) and Ca(3)(Y(0.5)Eu(0.5))(AlO)(3)(BO(3))(4) phosphors and matching blue-emitting phosphors. The results indicate that the quality of the brightness and color reproduction is suitable for application in shortwave UV fluorescent lamps. The white-light fluorescent lamp displays CIE chromaticity coordinates of x = 0.33, y = 0.35, a warm white light with a correlated color temperature of 5646 K, and a color-rendering index of Ra = 70.


Assuntos
Microscopia de Fluorescência/métodos , Espectrometria de Fluorescência/métodos , Óxido de Alumínio/química , Bário/química , Cálcio/química , Césio/química , Európio/química , Luz , Fósforo/química , Térbio/química , Raios Ultravioleta , Difração de Raios X , Ítrio/química
18.
Dalton Trans ; 39(24): 5676-82, 2010 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-20490402

RESUMO

Heterotrinuclear Zn(2)Ln (Ln = Nd 2, Eu 3, Tb 4, Er 5, Yb 6) clusters [(Znq(2))(2)](mu-CH(3)COO){Ln(hfac)(2)} (q = 8-hydroxylquinolinate, hfac = hexafluoroacetylacetonate) have been synthesized. The Zn(2)Ln framework is ligated by two q ligands featuring mu-phenoxo and two q ligands featuring mu(3)-phenoxo coordination modes, and one mu-CH(3)COO(-) anions. Since the short intramolecular separations of Zn...Ln (ca. 3.354-3.373 A) allow energy transfer from Znq(2)-based sensitizers to the Ln(III) centres through two energy transfer pathways, the lanthanide luminescence is indeed "lighted up" by excitation of the Znq(2)-based chromopores. Photophysical measurements revealed that these Zn(2)Ln complexes exhibit the so-called "dual emission" originating from both Znq(2)-based luminophores and lanthanide emitters. By virtue of the dual luminescence with complementary colours, the Znq(2)-based cyan emission and Eu(III)-centred red luminescence are combined to generate a white-light emission in the Zn(2)Eu (3) complex.


Assuntos
Complexos de Coordenação/síntese química , Elementos da Série dos Lantanídeos/química , Zinco/química , Complexos de Coordenação/química , Cristalografia por Raios X , Érbio/química , Európio/química , Hidrocarbonetos Fluorados/química , Conformação Molecular , Neodímio/química , Pentanonas/química , Espectrometria de Fluorescência , Térbio/química , Itérbio/química
19.
J Biomol Screen ; 15(8): 1008-15, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20460248

RESUMO

Identification and characterization of kinase inhibitor potency and selectivity is often an iterative process in which a library of compounds is first screened against a single kinase, and hits from that screen are then profiled against other kinases to determine specificity. By developing kinase assays that employ either a terbium- or a europium-based time-resolved fluorescence resonance energy transfer (TR-FRET) readout, one can take advantage of the distinct emission properties of these labels to develop assays for 2 kinases that can be performed simultaneously in the same well. This not only increases the information content provided per assay well but can immediately provide information on compound specificity. The authors have applied this strategy to the development of multiplexed assays for 2 examples systems: EGFR and IKKbeta, as well as lipid kinase family members mTOR and PIK3C3. They demonstrate the ability of these multiplexed assays to characterize selective kinase inhibitors in a dose-response mode, with no difference in results obtained from traditional single kinase assays performed separately.


Assuntos
Ensaios Enzimáticos/métodos , Európio/química , Transferência Ressonante de Energia de Fluorescência/métodos , Inibidores de Proteínas Quinases/isolamento & purificação , Térbio/química , Animais , Calibragem , Avaliação Pré-Clínica de Medicamentos/métodos , Avaliação Pré-Clínica de Medicamentos/normas , Ensaios Enzimáticos/normas , Receptores ErbB/metabolismo , Transferência Ressonante de Energia de Fluorescência/normas , Ensaios de Triagem em Larga Escala/métodos , Ensaios de Triagem em Larga Escala/normas , Humanos , Quinase I-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Proteínas Quinases/análise , Inibidores de Proteínas Quinases/farmacologia , Serina-Treonina Quinases TOR/metabolismo
20.
J Sep Sci ; 33(4-5): 509-15, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20162634

RESUMO

A new post-column derivatization system is described and applied to the determination of flavonoids in citric beverages after their separation by LC using a monolithic column. The derivatization involves the formation of the chelates of the analytes with aluminum (III) and terbium (III) in the presence of the surfactant SDS and the measurement of the terbium sensitized luminescence at lambda(ex) 360 and lambda(em) 545 nm. Naringin, hesperidin, quercetin, naringenin, and kaempferol have been chosen as analyte models. The large Stokes shift and the relatively long wavelength emission of terbium(III) can minimize interferences from background sample matrix, which usually emit at shorter wavelengths. Calibration graphs were constructed in the intervals 6.0-1700 ng/mL naringin, 9.8-1700 ng/mL hesperidin, 2.1-2000 ng/mL quercetin, 5.2-1500 ng/mL naringenin and 2.5-2000 ng/mL kaempferol, with regression coefficients higher than 0.9935 in all instances. The precision of the method, expressed as RSD%, was established at two concentration levels, with values of 1.3 and 4.7%, which corresponded to the minimal and maximal error zones of the calibration graphs. The practical usefulness of the method is demonstrated by the analysis of orange juices, which were diluted and directly injected into the chromatographic system, obtaining recoveries between 86.9 and 108.2%.


Assuntos
Alumínio/química , Cromatografia Líquida/instrumentação , Flavonoides/análise , Frutas/química , Extratos Vegetais/química , Térbio/química , Quelantes/química , Cromatografia Líquida/métodos , Flavonoides/química , Estrutura Molecular , Espectrometria de Fluorescência , Fatores de Tempo
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