RESUMEN
Glioblastoma (GBM), one of the deadliest brain tumors, accounts for approximately 50% of all primary malignant CNS tumors, therefore novel, highly effective remedies are urgently needed. Boron neutron capture therapy, which has recently repositioned as a promising strategy to treat high-grade gliomas, requires a conspicuous accumulation of boron atoms in the cancer cells. With the aim of selectively deliver sodium borocaptate (BSH, a 12 B atoms-including molecule already employed in the clinics) to GBM cells, we developed novel cell membrane-derived vesicles (CMVs), overcoming the limits of natural extracellular vesicles as drug carriers, while maintaining their inherent homing abilities that make them preferable to fully synthetic nanocarriers. Purified cell membrane fragments, isolated from patient-derived GBM stem-like cell cultures, were used to prepare nanosized CMVs, which retained some membrane proteins specific of the GBM parent cells and were devoid of potentially detrimental genetic material. In vitro tests evidenced the targeting ability of this novel nanosystem and ruled out any cytotoxicity. The CMVs were successfully loaded with BSH, by following two different procedures, i.e. sonication and electroporation, demonstrating their potential applicability in GBM therapy.
Asunto(s)
Terapia por Captura de Neutrón de Boro , Neoplasias Encefálicas , Membrana Celular , Glioblastoma , Humanos , Terapia por Captura de Neutrón de Boro/métodos , Glioblastoma/radioterapia , Glioblastoma/patología , Glioblastoma/terapia , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/patología , Membrana Celular/metabolismo , Borohidruros/química , Línea Celular Tumoral , Portadores de Fármacos/química , Nanopartículas/química , Compuestos de SulfhidriloRESUMEN
Boron neutron capture therapy (BNCT) is a cancer treatment modality based on the nuclear capture and fission reactions that occur when boron-10, a stable isotope, is irradiated with neutrons of the appropriate energy to produce boron-11 in an unstable form, which undergoes instantaneous nuclear fission to produce high-energy, tumoricidal alpha particles. The primary purpose of this review is to provide an update on the first drug used clinically, sodium borocaptate (BSH), by the Japanese neurosurgeon Hiroshi Hatanaka to treat patients with brain tumors and the second drug, boronophenylalanine (BPA), which first was used clinically by the Japanese dermatologist Yutaka Mishima to treat patients with cutaneous melanomas. Subsequently, BPA has become the primary drug used as a boron delivery agent to treat patients with several types of cancers, specifically brain tumors and recurrent tumors of the head and neck region. The focus of this review will be on the initial studies that were carried out to define the pharmacokinetics and pharmacodynamics of BSH and BPA and their biodistribution in tumor and normal tissues following administration to patients with high-grade gliomas and their subsequent clinical use to treat patients with high-grade gliomas. First, we will summarize the studies that were carried out in Japan with BSH and subsequently at our own institution, The Ohio State University, and those of several other groups. Second, we will describe studies carried out in Japan with BPA and then in the United States that have led to its use as the primary drug that is being used clinically for BNCT. Third, although there have been intense efforts to develop new and better boron delivery agents for BNCT, none of these have yet been evaluated clinically. The present report will provide a guide to the future clinical evaluation of new boron delivery agents prior to their clinical use for BNCT.
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Borohidruros , Compuestos de Boro , Terapia por Captura de Neutrón de Boro , Fenilalanina , Terapia por Captura de Neutrón de Boro/métodos , Humanos , Compuestos de Boro/uso terapéutico , Compuestos de Boro/farmacocinética , Compuestos de Boro/administración & dosificación , Borohidruros/química , Fenilalanina/análogos & derivados , Fenilalanina/administración & dosificación , Fenilalanina/uso terapéutico , Fenilalanina/farmacocinética , Neoplasias/radioterapia , Neoplasias/tratamiento farmacológico , Compuestos de Sulfhidrilo/uso terapéutico , Compuestos de Sulfhidrilo/administración & dosificación , Animales , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/tratamiento farmacológicoRESUMEN
The limited analgesic efficiency of magnesium restricts its application in pain management. Here, we report boron hydride (BH) with ion currents rectification activity that can enhance the analgesic efficiency of magnesium without the risks of drug tolerance or addiction. We synthesize MgB2, comprising hexagonal boron sheets alternating with Mg2+. In pathological environment, Mg2+ is exchanged by H+, forming two-dimensional borophene-analogue BH sheets. BH interacts with the charged cations via cation-pi interaction, leading to dynamic modulation of sodium and potassium ion currents around neurons. Additionally, released Mg2+ competes Ca2+ to inhibit its influx and neuronal excitation. In vitro cultured dorsal root neurons show a remarkable increase in threshold potential from the normal -35.9â mV to -5.9â mV after the addition of MgB2, indicating potent analgesic effect. In three typical pain models, including CFA-induced inflammatory pain, CINP- or CCI-induced neuropathic pain, MgB2 exhibits analgesic efficiency approximately 2.23, 3.20, and 2.0â times higher than clinical MgSO4, respectively, and even about 1.04, 1.66, and 1.95â times higher than morphine, respectively. The development of magnesium based intermetallic compounds holds promise in addressing the non-opioid medical need for pain relief.
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Magnesio , Magnesio/química , Animales , Nanoestructuras/química , Ratones , Analgésicos/química , Analgésicos/farmacología , Borohidruros/químicaRESUMEN
Nanoscale zerovalent iron synthesized using borohydride (B-NZVI) has been widely applied in environmental remediation in recent decades. However, the contribution of boron in enhancing the inherent reactivity of B-NZVI and its effectiveness in removing hexavalent chromium [Cr(VI)] have not been well recognized and quantified. To the best of our knowledge, herein, a core-shell structure of B-NZVI featuring an Fe-B alloy shell beneath the iron oxide shell is demonstrated for the first time. Alloyed boron can reduce H+, contributing to more than 35.6% of H2 generation during acid digestion of B-NZVIs. In addition, alloyed B provides electrons for Fe3+ reduction during Cr(VI) removal, preventing in situ passivation of the reactive particle surface. Meanwhile, the amorphous oxide shell of B-NZVI exhibits an increased defect density, promoting the release of Fe2+ outside the shell to reduce Cr(VI), forming layer-structured precipitates and intense Fe-O bonds. Consequently, the surface-area-normalized capacity and surface reaction rate of B-NZVI are 6.5 and 6.9 times higher than those of crystalline NZVI, respectively. This study reveals the importance of alloyed B in Cr(VI) removal using B-NZVI and presents a comprehensive approach for investigating electron pathways and mechanisms involved in B-NZVIs for contaminant removal.
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Borohidruros , Boro , Hierro , Hierro/química , Borohidruros/química , Boro/química , Cromo/química , Electrones , Aleaciones/químicaRESUMEN
The functional analysis of epitranscriptomic modifications in RNA is constrained by a lack of methods that accurately capture their locations and levels. We previously demonstrated that the RNA modification N4-acetylcytidine (ac4C) can be mapped at base resolution through sodium borohydride reduction to tetrahydroacetylcytidine (tetrahydro-ac4C), followed by cDNA synthesis to misincorporate adenosine opposite reduced ac4C sites, culminating in C:T mismatches at acetylated cytidines (RedaC:T). However, this process is relatively inefficient, resulting in <20% C:T mismatches at a fully modified ac4C site in 18S rRNA. Considering that ac4C locations in other substrates including mRNA are unlikely to reach full penetrance, this method is not ideal for comprehensive mapping. Here, we introduce "RetraC:T" (reduction to tetrahydro-ac4C and reverse transcription with amino-dATP to induce C:T mismatches) as a method with enhanced ability to detect ac4C in cellular RNA. In brief, RNA is reduced through NaBH4 or the closely related reagent sodium cyanoborohydride (NaCNBH3) followed by cDNA synthesis in the presence of a modified DNA nucleotide, 2-amino-dATP, that preferentially binds to tetrahydro-ac4C. Incorporation of the modified dNTP substantially improved C:T mismatch rates, reaching stoichiometric detection of ac4C in 18S rRNA. Importantly, 2-amino-dATP did not result in truncated cDNA products nor increase mismatches at other locations. Thus, modified dNTPs are introduced as a new addition to the toolbox for detecting ac4C at base resolution.
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Citidina , ADN Complementario , Citidina/análogos & derivados , Citidina/química , Citidina/metabolismo , Citidina/genética , ADN Complementario/genética , ARN/genética , ARN/química , ARN/metabolismo , Humanos , Borohidruros/química , Oxidación-Reducción , Transcripción Reversa , ARN Ribosómico 18S/genética , ARN Ribosómico 18S/metabolismoRESUMEN
NiO nanoparticles were synthesized from pine cone extract by green synthesis method, which is a simple, cost-effective, environmentally friendly and sustainable method. The particle size of NiO nanoparticles was determined to be in the range of 10-25 nm by X-diffraction differential and transmission electron microscope analysis, and the bandgap energy of NiO nanoparticles was determined to be 2.66 eV. The catalytic effect of NiO nanoparticles in both microwave-assisted sodium borohydride hydrolysis and photocatalytic reduction of methylene blue was examined and it was determined that they had a high catalytic effect in both applications. It was determined that the hydrogen production rate in sodium borohydride hydrolysis was 1135 mL/g/min. The activation energy of sodium borohydride hydrolysis is 29.69 kJ/mol and 29.59 kJ/mol for the nth-order and Langmuir Hinshelwood kinetic models, respectively. In the photocatalytic reduction of methylene blue with NaBH4, it was determined that the reduction did not occur in the absence of a catalyst, but in the presence of the catalyst, the reduction occurred 98% in 3 min. It was determined that NiO nanoparticles were used five times in the photocatalytic reduction of methylene blue and the reduction efficiency for the fifth time was 93%. It was determined that the photocatalytic reduction of methylene blue was pseudo-first order and the rate constant was 1.63 s-1. It was determined that NiO nanoparticles synthesized by the environmentally friendly green synthesis method can be used as catalysts for two different applications.
NiO nanoparticles were synthesized from pinecone extract in a simple, cost-effective, and green method. The synthesized NiO nanoparticles were characterized using various characterization techniques. NiO nanoparticles have high activity both in the photocatalytic reduction of methylene blue and in the hydrolysis of sodium borohydride, and they are catalysts with high activity in two different applications. Photocatalytic reduction of methylene blue with uncatalyzed NaBH4 was not achieved and was completed in 3 min in the presence of NiO nanoparticle catalyst. It was determined that the hydrogen production rate in sodium borohydride hydrolysis was 1135 mL/g/min. NiO nanoparticle catalysts have low activation energy for sodium borohydride hydrolysis.
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Borohidruros , Tecnología Química Verde , Azul de Metileno , Níquel , Azul de Metileno/química , Níquel/química , Borohidruros/química , Catálisis , Hidrólisis , Oxidación-Reducción , Pinus , Nanopartículas del Metal/químicaRESUMEN
Human head and neck squamous cell carcinoma cells transfected with mutant TP53 (SAS/mp53) or neo vector (SAS/neo) were inoculated subcutaneously into left hind legs of nude mice. After the subcutaneous administration of a 10B-carrier, boronophenylalanine-10B (BPA) or sodium mercaptododecaborate-10B (BSH), at two separate concentrations, the 10B concentrations in tumors were measured using γ-ray spectrometry. The tumor-bearing mice received 5-bromo-2'-deoxyuridine (BrdU) continuously to label all intratumor proliferating (P) tumor cells, then were administered with BPA or BSH. Subsequently, the tumors were irradiated with reactor neutron beams during the time of which 10B concentrations were kept at levels similar to each other. Following irradiation, cells from some tumors were isolated and incubated with a cytokinesis blocker. The responses of BrdU-unlabeled quiescent (Q) and total (= P + Q) tumor cells were assessed based on the frequencies of micronucleation using immunofluorescence staining for BrdU. In both SAS/neo and SAS/mp53 tumors, the compound biological effectiveness (CBE) values were higher in Q cells and in the use of BPA than total cells and BSH, respectively. The higher the administered concentrations were, the smaller the CBE values became, with a clearer tendency in SAS/neo tumors and the use of BPA than in SAS/mp53 tumors and BSH, respectively. The values for BPA that delivers into solid tumors more dependently on uptake capacity of tumor cells than BSH became more alterable. Tumor micro-environmental heterogeneity might partially influence on the CBE value. The CBE value can be regarded as one of the indices showing the level of intratumor heterogeneity.
Asunto(s)
Terapia por Captura de Neutrón de Boro , Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Animales , Ratones , Humanos , Bromodesoxiuridina/análisis , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/patología , Terapia por Captura de Neutrón de Boro/métodos , Ratones Desnudos , Compuestos de Boro/uso terapéutico , Borohidruros/química , Compuestos de Sulfhidrilo , Proteína p53 Supresora de TumorRESUMEN
In hydrolysis and electro-oxidation of the borohydride anion BH4-, key reactions in the field of energy, one critical short-living intermediate is BH3OH-. When water was used as both solvent and reactant, only BH3OH- is detected by 11B NMR. By moving away from such conditions and using DMF as solvent and water as reactant in excess, four 11B NMR quartets were observed. These signals were due to BH3-based intermediates as suggested by theoretical calculations; they were DMF·BH3, BH3OH-, and B2H7- (i.e., [H3B-H-BH3]- or [H4B-BH3]-). Our results shed light on the importance of BH3 stemming from BH4- and on its capacity as Lewis acid to interact with Lewis bases such as DMF, OH-, and BH4-. These findings are important for a better understanding at the molecular level of hydrolysis of BH4- and production of impurities in boranes synthesis.
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Boranos , Aniones , Borohidruros/química , Hidrólisis , AguaRESUMEN
Boron neutron capture therapy (BNCT) is a cancer-selective radiotherapy that utilizes the cancer targeting 10B-compound. Cancer cells that take up the compound are substantially damaged by the high liner energy transfer (LET) particles emitted mainly from the 10B(n, α7Li reaction. BNCT can minimize the dose to normal tissues, but it must be performed within the tolerable range of normal tissues. Therefore, it is important to evaluate the response of normal tissues to BNCT. Since BNCT yields a mixture of high and low LET radiations that make it difficult to understand the radiobiological basis of BNCT, it is important to evaluate the relative biological effectiveness (RBE) and compound biological effectiveness (CBE) factors for assessing the responses of normal tissues to BNCT. BSH and BPA are the only 10B-compounds that can be used for clinical BNCT. Their biological behavior and cancer targeting mechanisms are different; therefore, they affect the CBE values differently. In this review, we present the RBE and CBE values of BPA or BSH for normal tissue damage by BNCT irradiation. The skin, brain (spinal cord), mucosa, lung, and liver are included as normal tissues. The CBE values of BPA and BSH for tumor control are also discussed.
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Borohidruros/química , Terapia por Captura de Neutrón de Boro , Fenilalanina/química , Compuestos de Sulfhidrilo/química , Animales , Humanos , Neoplasias/patología , Neoplasias/radioterapia , Efectividad Biológica Relativa , Distribución TisularRESUMEN
OBJECTIVE: The paper presents the antibacterial activity of silver nanoparticles (AgNPs) when conjugated with Levofloxacin. The AgNPs used in this study were synthesized from silver nitrate using sodium borohydride as a reducing agent. MATERIALS AND METHODS: Levofloxacin activity was determined by minimum inhibitory concentrations (MICs) and also the erythrocyte hemolytic assay determined the capability of conjugation to cause hemolysis in human erythrocyte. RESULTS: The synthesis of levofloxacin-AgNP conjugates was confirmed by ultraviolet/visible (UV/vis) spectroscopy. A peak absorption value between 400-450 nm for the extract and the color change to dark brown were corresponding to the plasmon absorbance of AgNPs. On the other hand, levofloxacin-AgNPs could be effective against methicillin-resistant Staphylococcus aureus (MRSA). The MICs of levofloxacin and levofloxacin-AgNPs were 12 and 10 µM, respectively. CONCLUSIONS: These findings indicated that levofloxacin-AgNPs had an effective bactericidal activity against the bacterial MRSAs. This conjugation appeared to inhibit bacterial adaptive capabilities, which leads to inhibition of bacterial resistance.
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Antibacterianos/farmacología , Levofloxacino/farmacología , Nanopartículas del Metal , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Antibacterianos/administración & dosificación , Antibacterianos/toxicidad , Borohidruros/química , Hemólisis/efectos de los fármacos , Humanos , Levofloxacino/administración & dosificación , Levofloxacino/toxicidad , Pruebas de Sensibilidad Microbiana , Nitrato de Plata/químicaRESUMEN
Silver nanomaterials have attracted a great deal of interest due to their broad-spectrum antimicrobial activity. However, it is still challenging to balance the high antibacterial efficiency with low damage to biological cells of silver nanostructures, especially when the diameter decreases to less than 10 nm. Here, we developed a new type of Ag nanohybrid material via a unimolecular micelle template method, which presents amazing antibacterial activities and almost noncytotoxicity. First, water-soluble multiarm star-shaped brushlike copolymer α-CD-g-[(PEO40-g-PAA50)-b-PEO5]18 was precisely synthesized and its micelle behavior in different solvents was revealed. Then, nanocrystal clusters assembled by Ag grains (Ag@Template NCs) were prepared through an in situ redox route using the unimolecular micelle of α-CD-g-[(PEO40-g-PAA50)-b-PEO5]18 as the soft template, AgNO3 as a precursor, and tetrabutylammonium borohydride (TBAB) as the reducing agent. The overall size of the achieved Ag@Template NCs is controlled by the template structure at around 40 nm (Dh in DMF), and the size of the Ag grain can be easily regulated from â¼1 to â¼5 nm by adjusting the feeding ratio of AgNO3/acrylic acid (AA) units in the template from 1:10 to 1:1. Benefitting from the structural design of the template, all Ag@Template NCs prepared here exhibit excellent dispersibility and chemical stability in different aqueous environments (neutral, pH = 5.5, and 0.9% NaCl physiological saline solution), which play a crucial role in the long-term storage and potential application in a complex physiological environment. The antibacterial and cytotoxicity tests indicate that Ag@Template NCs display much better performance than Ag nanoparticles (Ag NPs), which have a comparable overall size of â¼25 nm. The inhibitory capability of Ag@Template NCs to bacteria strongly depends on the grain size. Specifically, the Ag@Template-1 NC assembled by the smallest grains (1.6 ± 0.3 nm) presents the best antibacterial activity. For E. coli (-), the MIC value is as low as 5 µg/mL (0.36 µg/mL of Ag), while for S. aureus (+), the value is around 10 µg/mL (0.72 µg/mL of Ag). The survival rate of L02 cells and lactate dehydrogenase assay together illustrate the low cytotoxicity possessed by the prepared Ag@Template NCs. Therefore, the proposed Ag@Template NC structure successfully resolves the high reactivity, instability, and fast oxidation issues of the ultrasmall Ag nanoparticles, and integrates high antibacterial efficiency and nontoxicity to biological cells into one platform, which implies its broad potential application in biomedicine.
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Antibacterianos/efectos adversos , Antibacterianos/química , Nanopartículas del Metal/química , Plata/química , Antibacterianos/metabolismo , Borohidruros/química , Supervivencia Celular/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Humanos , Pruebas de Sensibilidad Microbiana , Tamaño de la Partícula , Polímeros/química , Compuestos de Amonio Cuaternario/química , Staphylococcus aureus/efectos de los fármacos , Propiedades de Superficie , Nanomedicina TeranósticaRESUMEN
In this study, tin oxidecobalt oxide nanocatalyst was prepared by a simple method, which grew in spherical particles with an average diameter of 30 nm. Tin oxide-cobalt oxide was further wrapped in alginate polymer hydrogel (Alg@tin oxide-cobalt oxide), and both materials were utilized as nanocatalysts for the catalytic transformation of different pollutants. Tin oxide-cobalt oxide and Alg@tin oxide-cobalt oxide nanocatalysts were tested for the catalytic reduction of 4-nitrophenol, congo red, methyl orange, methylene blue (MB) and potassium ferricyanide in which sodium borohydride was used as a reducing agent. Tin oxide-cobalt oxide and Alg@tin oxide-cobalt oxide nanocatalysts synergistically reduced MB in shorter time (2.0 and 4.0 min) compared to other dyes. The reduction conditions were optimized by changing different parameters. The rate constants for MB reduction were calculated and found to be 1.5714 min-1 and 0.6033 min-1 using tin oxide-cobalt oxide and Alg@tin oxide-cobalt oxide nanocatalysts, respectively. Implementing Alg@tin oxide-cobalt oxide nanocatalyst toward MB reduction in real samples proved its efficacy in sea and well water samples. The catalyst could be easily recovered, recycled and revealed a minimal loss of nanoparticles, which offering a competition and replacement with reputable commercial catalysts.
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Alginatos/química , Cobalto/química , Nanocompuestos , Óxidos/química , Compuestos de Estaño/química , Aguas Residuales/química , Contaminantes Químicos del Agua/química , Purificación del Agua , Compuestos Azo/química , Borohidruros/química , Catálisis , Rojo Congo/química , Ferricianuros/química , Cinética , Azul de Metileno/química , Nanotecnología , Nitrofenoles/química , Oxidación-ReducciónRESUMEN
Nitroaromatic antibiotics are used to treat a variety of bacterial and parasitic infections. These prodrugs require reductive bioactivation for activity, which provides a pathway for the release of nitrogen oxide species such as nitric oxide, nitrite, and/or nitroxyl. Using sodium borohydride and 2-aminoethanol as model reductants, this work examines release of nitrogen oxide species from various nitroaromatic compounds through several characterization methods. Specifically, 4- and 5-nitroimidazoles reproducibly generate higher amounts of nitrite (not nitric oxide or nitroxyl) than 2-nitroimidazoles during the reaction of model hydride donors or thiols. Mass spectrometric analysis shows clean formation of products resulting from nucleophile addition and nitro group loss. 2-Nitrofurans generate nitrite upon addition of sodium borohydride or 2-aminoethanethiol, but these complex reactions do not produce clean organic products. A mechanism that includes nucleophile addition to the carbon ßto the nitro group to generate a nitronate anion followed by protonation and nitrous acid elimination explains the observed products and labeling studies. These systematic studies give a better understanding of the release mechanisms of nitrogen oxide species from these compounds allowing for the design of more efficient therapeutics.
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Antibacterianos/química , Borohidruros/química , Nitritos/química , Nitrocompuestos/química , Compuestos de Sulfhidrilo/química , Estructura MolecularRESUMEN
The presence of saccharin (SH) could be efficiently sensed (in the concentration range of 5 × 10-5 M to 5 × 10-1 M) through the interference synthesis of gum ghatti (GG) capped silver nanoparticles (GGAgNps). The synthesis used sodium borohydride and gum ghatti (GG) as the reducing and capping agents respectively. The strong hydrogen-bonding recognition between GG and SH was responsible for the interference. The intensity of the SPR peak of GGAgNps was found linearly dependent on [SH]. The SH detection was further enhanced when combo capping comprising of GG and chitosan (Ch) (in 1:1 weight ratio) was used while the use of gum acacia (GA) in place of Ch (in combo) decreased the detection sensitivity. The combo polysaccharide solutions had non-Newtonian behaviour and shear thinning property like GG. The method was also applied for the successful detection of SH in commercially available real juice samples.
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Nanopartículas del Metal/química , Gomas de Plantas/química , Sacarina/análisis , Plata/química , Borohidruros/química , Concentración de Iones de Hidrógeno , Nanopartículas del Metal/ultraestructura , Tamaño de la Partícula , Polisacáridos/química , Nitrato de Plata/química , Espectrofotometría Ultravioleta , Espectroscopía Infrarroja por Transformada de Fourier , Electricidad Estática , Edulcorantes/análisis , Factores de Tiempo , ViscosidadRESUMEN
Boron neutron capture therapy (BNCT), a binary cancer therapeutic modality, has moved to a new phase since development of accelerator-based neutron sources and establishment of BNCT centers in Finland and Japan. That stimulated efforts for better boron delivery agent development. As liposomes have shown effective boron delivery properties and sufficient tumor retention, fluorescent liposome labelling may serve as a rapid method to study initial ability of newly synthesized liposomes to be captured by tumor cells prior to experiments on boron accumulation and neutron irradiation. In this work, we studied the accumulation and biodistribution of pegylated liposomes with encapsulated borocaptate (BSH) and a fluorescent label (Nile Red) in U87 (human glioblastoma), SW-620 (human colon carcinoma), SK-MEL-28 (human melanoma), FetMSC (mesenchymal human embryo stem cells), and EMBR (primary embryocytes) cell lines as well as an orthotopic xenograft model of U87 glioma in SCID mice. Results indicate that fluorescent microscopy is effective at determining the intracellular localization of the liposomes using a fluorescent label. The synthesized, pegylated liposomes showed higher accumulation in tumors compared to normal cells, with characteristic concentration peaks in SW-620 and U87 cell lines, and provided in vivo tumor selectivity with several-fold higher tumor tissue fluorescence at the 6-h timepoint. Graphical abstract Fluorescent images of U-87 glioma cells after 24 hours of incubation with BSH-containing liposomes labeled with lipophilic Nile Red (red color)and water-soluble FITC-Dextran (green color); cell nuclei in blue color (DAPI-staining) (×400). Scale bar is 50 µm. Fluorescent labelling serves as anexpress method to study liposome delivery efficiency prior to boron accumulation evaluation and BNCT irradiation experiments.
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Borohidruros/química , Colorantes Fluorescentes/química , Liposomas/química , Borohidruros/uso terapéutico , Línea Celular Tumoral , Glioma/patología , HumanosRESUMEN
Cytonemes are specialized signalling filopodia that have a role in development and cellular differentiation. However, they are not well preserved by standard fixation techniques to study protein localization and interactions. A recent methodological advance has yielded improvements in cytoneme preservation using glutaraldehyde fixation and sodium borohydride treatment to reduce background. We herein describe a safer method for effective blocking using glycine following glutaraldehyde fixation of cytonemes on cultured adherent cells and demonstrate its effectiveness in immunocytochemistry.
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Comunicación Celular , Inmunohistoquímica , Seudópodos/metabolismo , Borohidruros/química , Adhesión Celular , Células Cultivadas , Glutaral/química , HumanosRESUMEN
Chitosan (Ch) capped Ch-CeO2, Ch-CeO2/Ag, Ch-CeO2/Pd and Ch-CeO2/Ag/Pd nanomaterials were fabricated using seedless and metal displacement plating method. The Ce4+ ions first formed complex with Ch through amino and hydroxyl groups and then reduced in presence of NaOH and molecular oxygen at higher temperature. Ch-Ag+ and Ch-Pd2+ complexes adsorbed on the surface of Ch-CeO2 and reduced under potential deposition. Ninhydrin reaction test was conducted to confirm the presence of chitosan on the surface of NMs. The catalytic efficiency was increases markedly with incorporating noble metal into Ch-CeO2 NMs. Ch-CeO2/Ag/Pd exhibits higher catalytic performance towards hydrogen generation due to the narrow band gap (2.65 eV) and smaller work function of CeO2 (Ï = 2.8 eV) than that of Ag0(Ï =4.6 eV) and Pd0 (Ï = 5.2 eV). Hydrogen generation rates increases with temperature and activation energies were found to be 63.2, 60.3, 56.2 and 53.0 kJ/mol for Ch-CeO2, Ch-CeO2/Ag, Ch-CeO2/Pd, and Ch-CeO2/Ag/Pd, respectively. CeO2/Ag/Pd shows better catalytic efficiency due to the strong interaction between Ag/Pd metal and active support CeO2. The photocatalytic rates drastically inhibited with scavengers, demonstrate that the reactive radical oxygen species (HO and O2-), holes (h+) and electrons (e-) played major role in the NaBH4 hydrolysis.
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Cerio/química , Quitosano/química , Nanoestructuras/química , Adsorción , Borohidruros/química , Catálisis , Entropía , Hidrógeno/química , Hidrólisis , Nanoestructuras/ultraestructura , Hidróxido de Sodio/química , Espectrometría por Rayos X , Espectrofotometría Ultravioleta , Luz Solar , Temperatura , ViscosidadRESUMEN
In a recent paper, we showed the difference between the first stage of the one-substrate and the two-substrate transketolase reactions - the possibility of transfer of glycolaldehyde formed as a result of cleavage of the donor substrate from the thiazole ring of thiamine diphosphate to its aminopyrimidine ring through the tricycle formation stage, which is necessary for binding and splitting the second molecule of donor substrate [O.N. Solovjeva et al., The mechanism of a one-substrate transketolase reaction, Biosci. Rep. 40 (8) (2020) BSR20180246]. Here we show that under the action of the reducing agent a tricycle accumulates in a significant amount. Therefore, a significant decrease in the reaction rate of the one-substrate transketolase reaction compared to the two-substrate reaction is due to the stage of transferring the first glycolaldehyde molecule from the thiazole ring to the aminopyrimidine ring of thiamine diphosphate. Fragmentation of the four-carbon thiamine diphosphate derivatives showed that two glycolaldehyde molecules are bound to both coenzyme rings and the erythrulose molecule is bound to a thiazole ring. It was concluded that in the one-substrate reaction erythrulose is formed on the thiazole ring of thiamine diphosphate from two glycol aldehyde molecules linked to both thiamine diphosphate rings. The kinetic characteristics were determined for the two substrates, fructose 6-phosphate and glycolaldehyde.
Asunto(s)
Transcetolasa/química , Transcetolasa/metabolismo , Acetaldehído/análogos & derivados , Acetaldehído/química , Acetaldehído/metabolismo , Biocatálisis , Borohidruros/química , Coenzimas/metabolismo , Fructosafosfatos/química , Fructosafosfatos/metabolismo , Cinética , Saccharomyces cerevisiae/enzimología , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/metabolismo , Espectrometría de Masa por Ionización de Electrospray , Especificidad por Sustrato , Tetrosas/metabolismo , Tiamina Pirofosfato/química , Tiamina Pirofosfato/metabolismoRESUMEN
The cationic Pt complex (Pt(NC6H4-C6H4N-(CH2)10-O(C6H3-3,5-(OMe)2)(MeN-(CH2CH2NMe2)2))+ was prepared by the reaction of alkylbipyridinium ligand with a nitrateplatinum(II) complex. Mixing the complex and α- and ß-cyclodextrins in aqueous media produced the corresponding [2]rotaxanes with 1:1 stoichiometry. γ-Cyclodextrin and the Pt complex formed a rotaxane having components in a 1:1 or 2:1 molar ratio. The results of mass and nuclear magnetic resonance (NMR) measurements confirmed the rotaxane structures of the Pt complexes. Transmission electron microscopy (TEM) and atomic force microscope (AFM) analyses revealed the formation of micelles or vesicles. The addition of NaBH4 to the rotaxanes in aqueous media formed Pt nanoparticles with diameters of 1.3-2.8 nm, as characterized by TEM. The aggregated size of the nanoparticles formed from the rotaxane did not change even at 70 °C, and they showed higher thermal stability than those obtained from the reduction of the cyclodextrin-free Pt complex.
Asunto(s)
Ciclodextrinas/química , Nanopartículas del Metal/química , Compuestos Organoplatinos/química , Platino (Metal)/química , Rotaxanos/química , Borohidruros/química , Ligandos , Micelas , Microscopía de Fuerza Atómica , Microscopía Electrónica de Transmisión , Conformación Molecular , Compuestos Organoplatinos/síntesis química , Tamaño de la Partícula , Espectroscopía de Protones por Resonancia Magnética , Soluciones , Espectrofotometría , TemperaturaRESUMEN
Application of organometallic ruthenium(II) arene complexes has been successful for the modulation of cellular redox processes via their interaction with species such as formate to control the NAD+/NADH balance in cells. Here we present the first evidence that similar effects can be reached with the application of a nonorganometallic ruthenium(II) polypyridyl complex. Kinetic studies performed demonstrate the ability of [RuII(terpy)(en)(H2O/EtOH)]2+ in water/ethanol (1:9, v/v) solution, where terpy = 2,2':6',2â³-terpyridine and en = ethylenediamine, to catalyze the reduction of the NAD+ coenzyme to NADH in the presence of formate as hydride transfer source. In this case, terpy instead of arene is responsible for the labilization of coordinated solvent. The suggested catalytic cycle begins with the fast anation of the [RuII(terpy)(en)(H2O/EtOH)]2+ complex by formate. This is followed by the rate-determining formate-catalyzed decarboxylation of the generated ruthenium(II) formato complex to form [RuII(terpy)(en)H]+. Rapid hydride transfer to NAD+ from [RuII(terpy)(en)H]+ to form NADH and to regenerate the starting ruthenium(II) solvato complex, closes the overall catalytic cycle.