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1.
Biosens Bioelectron ; 169: 112578, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32911317

RESUMO

The ongoing global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to active research in its associated diagnostics and medical treatments. While quantitative reverse transcription polymerase chain reaction (qRT-PCR) is the most reliable method to detect viral genes of SARS-CoV-2, serological tests for specific antiviral antibodies are also important as they identify false negative qRT-PCR responses, track how effectively the patient's immune system is fighting the infection, and are potentially helpful for plasma transfusion therapies. In this work, based on the principle of localized surface plasmon resonance (LSPR), we develop an opto-microfluidic sensing platform with gold nanospikes, fabricated by electrodeposition, to detect the presence and amount of antibodies specific to the SARS-CoV-2 spike protein in 1µL of human plasma diluted in 1mL of buffer solution, within ∼30min. The target antibody concentration can be correlated with the LSPR wavelength peak shift of gold nanospikes caused by the local refractive index change due to the antigen-antibody binding. This label-free microfluidic platform achieves a limit of detection of ∼0.08ng/mL (∼0.5pM), falling under the clinical relevant concentration range. We demonstrate that our opto-microfluidic platform offers a promising point-of-care testing tool to complement standard serological assays and make SARS-CoV-2 quantitative diagnostics easier, cheaper, and faster.


Assuntos
Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , Infecções por Coronavirus/sangue , Nanoestruturas/química , Pneumonia Viral/sangue , Glicoproteína da Espícula de Coronavírus/imunologia , Ressonância de Plasmônio de Superfície/instrumentação , Anticorpos Antivirais/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Desenho de Equipamento , Ouro/química , Humanos , Dispositivos Lab-On-A-Chip , Limite de Detecção , Nanoestruturas/ultraestrutura , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/virologia
2.
Nat Commun ; 11(1): 4530, 2020 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-32913195

RESUMO

Various cancer cells have been demonstrated to have the capacity to form plasmonic gold nanoparticles when chloroauric acid is introduced to their cellular microenvironment. But their biomedical applications are limited, particularly considering the millimolar concentrations and longer incubation period of ionic gold. Here, we describe a simplistic method of intracellular biomineralization to produce plasmonic gold nanoparticles at micromolar concentrations within 30 min of application utilizing polyethylene glycol as delivery vector for ionic gold. We have characterized this process for intracellular gold nanoparticle formation, which progressively accumulates proteins as the ionic gold clusters migrate to the nucleus. This nano-vectorized application of ionic gold emphasizes its potential biomedical opportunities while reducing the quantity of ionic gold and required incubation time. To demonstrate its biomedical potential, we further induce in-situ biosynthesis of gold nanoparticles within MCF7 tumor mouse xenografts which is followed by its photothermal remediation.


Assuntos
Cloretos/administração & dosagem , Portadores de Fármacos/química , Compostos de Ouro/administração & dosagem , Ouro/química , Nanopartículas Metálicas/química , Neoplasias/tratamento farmacológico , Nanomedicina Teranóstica/métodos , Animais , Biomineralização/efeitos da radiação , Feminino , Ouro/efeitos da radiação , Humanos , Hipertermia Induzida/métodos , Íons , Células MCF-7 , Nanopartículas Metálicas/efeitos da radiação , Camundongos , Fotoquimioterapia/métodos , Polietilenoglicóis/química , Ensaios Antitumorais Modelo de Xenoenxerto
3.
Int J Nanomedicine ; 15: 4811-4824, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32753867

RESUMO

Purpose: Magnetic resonance imaging (MRI) contrast agents are pharmaceuticals that enable a better visualization of internal body structures. In this study, we present the synthesis, MRI signal enhancement capabilities, in vitro as well as in vivo cytotoxicity results of gold-coated iron oxide nanoparticles (Fe3O4@AuNPs) as potential contrast agents. Methods: Fe3O4@AuNPs were obtained by synthesizing iron oxide nanoparticles and gradually coating them with gold. The obtained Fe3O4@AuNPs were characterized by spectroscopies, transmission electron microscopy (TEM) and energy dispersive X-ray diffraction. The effect of the nanoparticles on the MRI signal was tested using a 7T Bruker PharmaScan system. Cytotoxicity tests were made in vitro on Fe3O4@AuNP-treated retinal pigment epithelium cells by WST-1 tests and in vivo by following histopathological changes in rats after injection of Fe3O4@AuNPs. Results: Stable Fe3O4@AuNPs were successfully prepared following a simple and fast protocol (<1h worktime) and identified using TEM. The cytotoxicity tests on cells have shown biocompatibility of Fe3O4@AuNPs at small concentrations of Fe (<1.95×10-8 mg/cell). Whereas, at higher Fe concentrations (eg 7.5×10-8 mg/cell), cell viability decreased to 80.88±5.03%, showing a mild cytotoxic effect. MRI tests on rats showed an optimal Fe3O4@AuNPs concentration of 6mg/100g body weight to obtain high-quality images. The histopathological studies revealed significant transient inflammatory responses in the time range from 2 hours to 14 days after injection and focal cellular alterations in several organs, with the lung being the most affected organ. These results were confirmed by hyperspectral microscopic imaging of the same, but unstained tissues. In most organs, the inflammatory responses and sublethal cellular damage appeared to be transitory, except for the kidneys, where the glomerular damage indicated progression towards glomerular sclerosis. Conclusion: The obtained stable, gold covered, iron oxide nanoparticles with reduced cytotoxicity, gave a negative T2 signal in the MRI, which makes them suitable for candidates as contrast agent in small animal MRI applications.


Assuntos
Meios de Contraste/química , Compostos Férricos/química , Ouro/química , Imagem por Ressonância Magnética , Nanopartículas Metálicas/química , Animais , Sobrevivência Celular , Endocitose , Inflamação/patologia , Masculino , Nanopartículas Metálicas/ultraestrutura , Ratos Wistar , Difração de Raios X
4.
Ther Deliv ; 11(8): 521-534, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32757745

RESUMO

Nanoscale size-dependent properties give nanomaterials unique specifications that are robust in many applications of human medicine. Gold nanoparticles (AuNPs) have recently gained attention because of their unique optical, physical and electrical properties. AuNPs increase the efficacy of biomedical applications in diagnostic treatments for infectious diseases, by targeting or labeling target cells/bioactive compounds. However, it is imperative to develop the regimens for more accurate diagnostic tools, preventive care and effective therapy. Our critical and comprehensive review presents emerging avenues of molecular diagnostics as well as therapeutics translated into clinical approaches. This manuscript critically reviews the rampant future of AuNPs in the diagnosis and treatment of the most important diseases, such as cancer and viruses of respiratory system.


Assuntos
Ouro/química , Nanopartículas Metálicas/química , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Portadores de Fármacos/química , Humanos , Pneumopatias/diagnóstico , Pneumopatias/terapia , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Pandemias , Fototerapia , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Pneumonia Viral/virologia
5.
Chem Commun (Camb) ; 56(70): 10235-10238, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32756614

RESUMO

Here, we report for the first time DNA aptamers targeted toward the COVID-19 nucleocapsid protein (Np). Np is one of the most abundant structural proteins and it serves as a diagnostic marker for the accurate and sensitive detection of COVID-19. After five rounds of selection, we obtained four DNA sequences with an affinity below 5 nM. The best one displayed a superb binding performance toward Np with a Kd value of 0.49 nM. Interestingly, we found that the four pairs of aptamers could bind to Np successively, suggesting a sandwich-type interaction. Using these sandwiched aptamers in ELISA and colloidal gold immunochromatographic strips, we were able to detect Np at the tens of pM level. The results demonstrate that aptamers are powerful molecular tools for virus detection, diagnosis, and antiviral therapy.


Assuntos
Aptâmeros de Nucleotídeos/metabolismo , Betacoronavirus/metabolismo , Proteínas do Nucleocapsídeo/metabolismo , Aptâmeros de Nucleotídeos/química , Sequência de Bases , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/diagnóstico , Ensaio de Imunoadsorção Enzimática/métodos , Ouro/química , Humanos , Cinética , Limite de Detecção , Nanopartículas Metálicas/química , Proteínas do Nucleocapsídeo/química , Pandemias , Pneumonia Viral/diagnóstico , Técnica de Seleção de Aptâmeros
6.
Int J Nanomedicine ; 15: 5005-5016, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764932

RESUMO

Background and Aim: With the wide applications of chitosan and gold nanoparticles in drug delivery and many consumer products, there is limited available information about their effects on drug-metabolizing enzymes (DMEs). Changes in DMEs could result in serious drug interactions. Therefore, this study aimed to investigate the effects of exposure to chitosan or gold nanoparticles on hepatic Phase I and II DMEs, liver function and integrity, oxidative damage and liver architecture in male rats. Methods: Animals were divided into three equal groups: a control group, a group treated with chitosan nanoparticles (200 mg/kg, 50±5 nm) and a group treated with gold nanoparticles (4 mg/kg, 15±5 nm). Rats were orally administered their respective doses daily for 10 days. Results: Both chitosan and gold nanoparticles decreased the body weights by more than 10%. Gold nanoparticles reduced the activities of antioxidants (superoxide dismutase and catalase), and reduced glutathione level and elevated the malondialdehyde level in the liver. Gold nanoparticles caused significant reductions in CYP1A1, CYP2E1, quinone oxidoreductase1, and glutathione S-transferase and elevated CYP2D6 and N-acetyl transferase2. Chitosan elevated CYP2E1 and CYP2D6 and reduced UDP-glucuronosyltransferase 1A1. Both nanoparticles disturbed the architecture of the liver, but the deleterious effects after gold nanoparticles treatment were more prominent. Conclusion: Taken together, gold nanoparticles severely perturbed the DMEs and would result in serious interactions with many drugs, herbs, and foods.


Assuntos
Antioxidantes/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Inativação Metabólica/efeitos dos fármacos , Fígado/efeitos dos fármacos , Nanopartículas Metálicas/efeitos adversos , Animais , Catalase/genética , Catalase/metabolismo , Quitosana/química , Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP2E1/genética , Citocromo P-450 CYP2E1/metabolismo , Interações Medicamentosas , Glucuronosiltransferase/genética , Glucuronosiltransferase/metabolismo , Glutationa/metabolismo , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Ouro/química , Ouro/farmacocinética , Fígado/metabolismo , Fígado/patologia , Masculino , Malondialdeído/metabolismo , Nanopartículas Metálicas/química , Ratos Wistar , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo
7.
PLoS One ; 15(8): e0237709, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32817653

RESUMO

OBJECTIVES: In this paper, we aim to detail the setup of a high spatio-temporal resolution, electrical recording system utilising planar microelectrode arrays with simultaneous optical imaging suitable for evaluating microelectrode performance with a proposed 'performance factor' metric. METHODS: Techniques that would facilitate low noise electrical recordings were coupled with voltage sensitive dyes and neuronal activity was recorded both electrically via a customised amplification system and optically via a high speed CMOS camera. This technique was applied to characterise microelectrode recording performance of gold and poly(3,4-ethylenedioxythiophene)/polystyrene sulfonate (PEDOT/PSS) coated electrodes through traditional signal to noise (SNR) calculations as well as the proposed performance factor. RESULTS: Neuronal activity was simultaneously recorded using both electrical and optical techniques and this activity was confirmed via tetrodotoxin application to inhibit action potential firing. PEDOT/PSS outperformed gold using both measurements, however, the performance factor metric estimated a 3 fold improvement in signal transduction when compared to gold, whereas SNR estimated an 8 fold improvement when compared to gold. CONCLUSION: The design and functionality of a system to record from neurons both electrically, through microelectrode arrays, and optically via voltage sensitive dyes was successfully achieved. SIGNIFICANCE: The high spatiotemporal resolution of both electrical and optical methods will allow for an array of applications such as improved detection of subthreshold synaptic events, validation of spike sorting algorithms and a provides a robust evaluation of extracellular microelectrode performance.


Assuntos
Potenciais de Ação/fisiologia , Eletrodos Implantados , Microeletrodos , Neurônios/fisiologia , Algoritmos , Ouro/química , Humanos , Polímeros/química , Transdução de Sinais/fisiologia
8.
ACS Sens ; 5(9): 2747-2752, 2020 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-32820626

RESUMO

With the current intense need for rapid and accurate detection of viruses due to COVID-19, we report on a platform technology that is well suited for this purpose, using intact measles virus for a demonstration. Cases of infection due to the measles virus are rapidly increasing, yet current diagnostic tools used to monitor for the virus rely on slow (>1 h) technologies. Here, we demonstrate the first biosensor capable of detecting the measles virus in minutes with no preprocessing steps. The key sensing element is an electrode coated with a self-assembled monolayer containing the measles antibody, immobilized through an N-heterocyclic carbene (NHC). The intact virus is detected by changes in resistance, giving a linear response to 10-100 µg/mL of the intact measles virus without the need to label or process the sample. The limit of detection is 6 µg/mL, which is at the lower limit of concentrations that can cause infections in primates. The NHC-based biosensors are shown to be superior to thiol-based systems, producing an approximately 10× larger response and significantly greater stability toward repeated measurements and long-term storage. This NHC-based biosensor thus represents an important development for both the rapid detection of the measles virus and as a platform technology for the detection of other biological targets of interest.


Assuntos
Anticorpos Imobilizados/imunologia , Benzimidazóis/química , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Vírus do Sarampo/isolamento & purificação , Anticorpos Imobilizados/química , Técnicas Eletroquímicas/instrumentação , Eletrodos , Ouro/química , Limite de Detecção , Vírus do Sarampo/imunologia
9.
Ecotoxicol Environ Saf ; 204: 111107, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32823057

RESUMO

Heavy metal pollution in marine environment poses a severe threat to the safety of marine products and is thus causing increasingly concerns in terms of their toxicity and potential health risks pose to human. Due to the complex matrix of marine products, a fast screening method for heavy metals at trace level with low price, reusability, high accuracy and long lifetime is of urgency and necessity for consumers and processing factories. This work described a simplified screening system through the preparation, characterization and particular application of Au nano particle sensor (AuNPS) in the complex marine matrix, the main aim is to significantly increase the stability, sensitivity and lifetime of detection system dedicated to Cu and Hg trace analysis in marine products. It is worth mentioning that, the proposed screening system was characterized through electrochemical experiments and theoretical calculations, which could be a new evidence for selecting the detection system in commercially complex samples. Importantly, the discipline of deposition and oxidative stripping process on AuNPS was explained based on the mechanism of Metal Ion Deficient Layer (MIDL), and illustrated with SEM changes during stripping process, as well as the dissolving-out rate of metals on AuNPS material. Moreover, to further improve the reusability and stability of AuNPS sensor, the complex marine matrix was purified by pre-plating interferences on indium tin oxide glass electrode. The screening system exhibited a liner response in the range of 0.02-0.10 µg mL-1 for Hg, 0.01-0.10 µg mL-1 and 0.001-0.01 µg mL-1 for Cu with the detection limits of 0.138 mg kg-1 and 1.51 mg kg-1 in marine matrix, respectively. The sensitivity and lifetime was at least two times better as compared to similar works even after 20-times use. Finally, this proposed analysis system combined with purification procedure was successfully applied for the edible and medicinal marine products analysis, meanwhile, the accuracy and stability were confirmed with standard analytical methods.


Assuntos
Análise de Alimentos/métodos , Nanopartículas Metálicas/química , Metais Pesados/análise , Eletrodos , Contaminação de Alimentos , Ouro/química , Humanos , Mercúrio/análise , Compostos de Estanho , Oligoelementos
10.
Int J Nanomedicine ; 15: 4969-4990, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764930

RESUMO

Background: Polyphenols possess antioxidant, anti-inflammatory and antimicrobial properties and have been used in the treatment of skin wounds and burns. We previously showed that tannic acid-modified AgNPs sized >26 nm promote wound healing, while tannic acid-modified AgNPs sized 13 nm can elicit strong local inflammatory response. In this study, we tested bimetallic Au@AgNPs sized 30 nm modified with selected flavonoid and non-flavonoid compounds for wound healing applications. Methods: Bimetallic Au@AgNPs were obtained by growing an Ag layer on AuNPs and further modified with selected polyphenols. After toxicity tests and in vitro scratch assay in HaCaT cells, modified lymph node assay as well as the mouse splint wound model were further used to access the wound healing potential of selected non-toxic modifications. Results: Tannic acid, gallic acid, polydatin, resveratrol, catechin, epicatechin, epigallocatechin, epicatechin gallate, epigallocatechin gallate and procyanidin B2 used to modify Au@AgNPs exhibited good toxicological profiles in HaCaT cells. Au@AgNPs modified with 15 µM tannic acid, 200 µM resveratrol, 200 µM epicatechin gallate, 1000 µM gallic acid and 200 µM procyanidin B2 induced wound healing in vivo and did not lead to the local irritation or inflammation. Tannic acid-modified Au@AgNPs induced epithelial-to-mesenchymal transition (EMT) - like re-epithelialization, while other polyphenol modifications of Au@AgNPs acted through proliferation and wound closure. Conclusion: Bimetallic Au@AgNPs can be used as a basis for modification with selected polyphenols for topical uses. In addition, we have demonstrated that particular polyphenols used to modify bimetallic nanoparticles may show different effects upon different stages of wound healing.


Assuntos
Ouro/química , Nanopartículas Metálicas/química , Polifenóis/química , Polifenóis/farmacologia , Prata/química , Cicatrização/efeitos dos fármacos , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Biflavonoides/química , Catequina/análogos & derivados , Catequina/química , Camundongos , Proantocianidinas/química , Taninos/química
11.
Nat Protoc ; 15(9): 2980-3008, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32839575

RESUMO

High-surface-area mesoporous materials expose abundant functional sites for improved performance in applications such as gas storage/separation, catalysis, and sensing. Recently, soft templates composed of amphiphilic surfactants and block copolymers have been used to introduce mesoporosity in various materials, including metals, metal oxides and carbonaceous compounds. In particular, mesoporous metals are attractive in electrocatalysis because their porous networks expose numerous unsaturated atoms on high-index facets that are highly active in catalysis. In this protocol, we describe how to create mesoporous metal films composed of gold, palladium, or platinum using block copolymer micelle templates. The amphiphilic block copolymer micelles are the sacrificial templates and generate uniform structures with tunable pore sizes in electrodeposited metal films. The procedure describes the electrodeposition in detail, including parameters such as micelle diameters, deposition potentials, and deposition times to ensure reproducibility. The micelle diameters can be controlled by swelling the micelles with different solvent mixtures or by using block copolymer micelles with different molecular weights. The deposition potentials and deposition times allow further control of the mesoporous structure and its thickness, respectively. Procedures for example applications are included: glucose oxidation, ethanol oxidation and methanol oxidation reactions. The synthetic methods for preparation of mesoporous metal films will take ~4 h; the subsequent electrochemical tests will take ~5 h for glucose sensing and ~3 h for alcohol oxidation reaction.


Assuntos
Ouro/química , Paládio/química , Platina/química , Álcoois/química , Catálise , Técnicas de Química Sintética , Eletroquímica , Interações Hidrofóbicas e Hidrofílicas , Micelas , Modelos Moleculares , Conformação Molecular , Oxirredução , Polímeros/química
12.
Int J Nanomedicine ; 15: 4151-4169, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606670

RESUMO

Purpose: Focused ultrasound (FUS) is a noninvasive method to produce thermal and mechanical destruction along with an immune-stimulatory effect against cancer. However, FUS ablation alone appears insufficient to generate consistent antitumor immunity. In this study, a multifunctional nanoparticle was designed to boost FUS-induced immune effects and achieve systemic, long-lasting antitumor immunity, along with imaging and thermal enhancement. Materials and Methods: PEGylated PLGA nanoparticles encapsulating astragalus polysaccharides (APS) and gold nanorods (AuNRs) were constructed by a simple double emulsion method, characterized, and tested for cytotoxicity. The abilities of PA imaging and thermal-synergetic ablation efficiency were analyzed in vitro and in vivo. The immune-synergistic effect on dendritic cell (DC) differentiation in vitro and the immune response in vivo were also evaluated. Results: The obtained APS/AuNR/PLGA-PEG nanoparticles have an average diameter of 255.00±0.1717 nm and an APS-loading efficiency of 54.89±2.07%, demonstrating their PA imaging capability and high biocompatibility both in vitro and in vivo. In addition, the as-prepared nanoparticles achieved a higher necrosis cell rate and induced apoptosis rate in an in vitro cell suspension assay, greater necrosis area and decreased energy efficiency factor (EEF) in an in vivo rabbit liver assay, and remarkable thermal-synergic performance. In particular, the nanoparticles upregulated the expression of MHC-II, CD80 and CD86 on cocultured DCs in vitro, followed by declining phagocytic function and enhanced interleukin (IL)-12 and interferon (INF)-γ production. Furthermore, they boosted the production of tumor necrosis factor (TNF)-α, IFN-γ, IL-4, IL-10, and IgG1 (P< 0.001) but not IgG2a. Immune promotion peaked on day 3 after FUS in vivo. Conclusion: The multifunctional APS/AuNR/PLGA-PEG nanoparticles can serve as an excellent synergistic agent for FUS therapy, facilitating real-time imaging, promoting thermal ablation effects, and boosting FUS-induced immune effects, which have the potential to be used for further clinical FUS treatment.


Assuntos
Astrágalo (Planta)/química , Neoplasias da Mama/terapia , Ouro/química , Nanopartículas Multifuncionais/química , Nanotubos/química , Polissacarídeos/química , Terapia por Ultrassom , Animais , Antígenos CD/metabolismo , Apoptose , Morte Celular , Diferenciação Celular , Linhagem Celular Tumoral , Proliferação de Células , Citocinas/metabolismo , Células Dendríticas/citologia , Feminino , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Imunoglobulina G/metabolismo , Linfócitos do Interstício Tumoral/imunologia , Camundongos Endogâmicos BALB C , Fagocitose , Técnicas Fotoacústicas , Poliésteres/síntese química , Poliésteres/química , Polietilenoglicóis/síntese química , Polietilenoglicóis/química , Coelhos , Nanomedicina Teranóstica , Fator A de Crescimento do Endotélio Vascular/metabolismo
13.
Analyst ; 145(16): 5638-5646, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32638712

RESUMO

An evaluation of a rapid portable gold-nanotechnology measuring SARS-CoV-2 IgM, IgA and IgG antibody concentrations against spike 1 (S1), spike 2 (S) and nucleocapsid (N) was conducted using serum samples from 74 patients tested for SARS-CoV-2 RNA on admission to hospital, and 47 historical control patients from March 2019. 59 patients were RNA(+) and 15 were RNA(-). A serum (±) classification was derived for all three antigens and a quantitative serological profile was obtained. Serum(+) was identified in 30% (95% CI 11-48) of initially RNA(-) patients, in 36% (95% CI 17-54) of RNA(+) patients before 10 days, 77% (95% CI 67-87) between 10 and 20 days and 95% (95% CI 86-100) after 21 days. The patient-level diagnostic accuracy relative to RNA(±) after 10 days displayed 88% sensitivity (95% CI 75-95) and 75% specificity (95% CI 22-99), although specificity compared with historical controls was 100% (95%CI 91-100). This study provides robust support for further evaluation and validation of this novel technology in a clinical setting and highlights challenges inherent in assessment of serological tests for an emerging disease such as COVID-19.


Assuntos
Anticorpos Antivirais/análise , Betacoronavirus/imunologia , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Testes Sorológicos/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/imunologia , Técnicas de Laboratório Clínico , Estudos de Coortes , Infecções por Coronavirus/sangue , Reações Falso-Negativas , Feminino , Ouro/química , Humanos , Imunoglobulina A/análise , Imunoglobulina A/imunologia , Imunoglobulina G/análise , Imunoglobulina G/imunologia , Imunoglobulina M/análise , Imunoglobulina M/imunologia , Masculino , Nanopartículas Metálicas/química , Pessoa de Meia-Idade , Proteínas do Nucleocapsídeo/imunologia , Pandemias , Pneumonia Viral/sangue , Sensibilidade e Especificidade , Glicoproteína da Espícula de Coronavírus/imunologia , Adulto Jovem
14.
Int J Nanomedicine ; 15: 4063-4078, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606664

RESUMO

Background: Among various theories for the origin of cancer, the "stemness phenotype model" suggests a dynamic feature for tumor cells in which non-cancer stem cells (non-CSCs) can inter-convert to CSCs. Differentiation with histone-deacetylase inhibitor, vorinostat (SAHA), can induce stem cells to differentiate as well as enforces non-CSCs to reprogram to CSCs. To avoid this undesirable effect, one can block the Wnt-ßcatenin pathway. Thus, a dual delivery system of SAHA and a Wnt-ßcatenin blocker will be beneficial in the induction of differentiation of CSCs. Protein corona (PC) formation in nanoparticle has a biologic milieu, and despite all problematic properties, it can be employed as a medium for dual loading of the drugs. Materials and Methods: We prepared sphere gold nanoparticles (GNPs) with human plasma protein corona loaded with SAHA as differentiating agent and PKF118-310 (PKF) as a Wnt-ßcatenin antagonist. The MCF7 breast cancer stem cells were treated with NPs and the viability and differentiation were evaluated by Western blotting and sphere formation assay. Results: We found that both drugs loaded onto corona-capped GNPs had significant cytotoxicity in comparison to bare GNP-corona. Data demonstrated an increase in stem cell population and upregulation of mesenchymal marker, Snail by SAHA-loaded GNPs treatment; however, the combination of PKF loaded GNPs along with SAHA-loaded GNPs resulted in a reduction of stem cell populations and Snail marker. We have shown that in MCF7 and its CSCs simultaneous treatment with SAHA and PKF118-310 induced differentiation and inhibition of Snail induction. Conclusion: Our study reveals the PC-coated GNPs as a biocompatible career for both hydrophilic (PKF) and hydrophobic (SAHA) agents which can decrease breast cancer stem cell populations along with reduced stemness state regression.


Assuntos
Neoplasias da Mama/patologia , Carcinogênese/patologia , Ouro/química , Nanopartículas Metálicas/química , Células-Tronco Neoplásicas/patologia , Coroa de Proteína/química , Vorinostat/farmacologia , Proteínas Wnt/antagonistas & inibidores , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Carcinogênese/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Liberação Controlada de Fármacos , Endocitose/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Inibidores de Histona Desacetilases/farmacologia , Humanos , Células MCF-7 , Nanosferas/química , Células-Tronco Neoplásicas/efeitos dos fármacos , Espectrofotometria Ultravioleta , Proteínas Wnt/metabolismo , beta Catenina/antagonistas & inibidores , beta Catenina/metabolismo
15.
Life Sci ; 257: 118081, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32663576

RESUMO

Temporal lobe epilepsy (TLE) is the most common form of epilepsy with focal seizures, and currently available drugs may fail to provide a thorough treatment of the patients. The present study demonstrates the utility of glucose-coated gold nanoparticles (GNPs) as selective carriers of an antiepileptic drug, lacosamide (LCM), in developing a strategy to cross the blood-brain barrier to overcome drug resistance. Intravenous administration of LCM-loaded GNPs to epileptic animals yielded significantly higher nanoparticle levels in the hippocampus compared to the nanoparticle administration to intact animals. The amplitude and frequency of EEG-waves in both ictal and interictal stages decreased significantly after LCM-GNP administration to animals with TLE, while a decrease in the number of seizures was also observed though statistically insignificant. In these animals, malondialdehyde was unaffected, and glutathione levels were lower in the hippocampus compared to sham. Ultrastructurally, LCM-GNPs were observed in the brain parenchyma after intravenous injection to animals with TLE. We conclude that glucose-coated GNPs can be efficient in transferring effective doses of LCM into the brain enabling elimination of the need to administer high doses of the drug, and hence, may represent a new approach in the treatment of drug-resistant TLE.


Assuntos
Anticonvulsivantes/administração & dosagem , Sistemas de Liberação de Medicamentos , Epilepsia do Lobo Temporal/tratamento farmacológico , Lacosamida/administração & dosagem , Nanopartículas Metálicas , Animais , Anticonvulsivantes/farmacocinética , Anticonvulsivantes/farmacologia , Encéfalo/metabolismo , Modelos Animais de Doenças , Eletroencefalografia , Ouro/química , Hipocampo/metabolismo , Injeções Intravenosas , Lacosamida/farmacocinética , Lacosamida/farmacologia , Masculino , Ratos , Ratos Wistar , Distribuição Tecidual
16.
Food Chem ; 332: 127376, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32615382

RESUMO

In this work, a molecularly imprinted sensor employing copper sulfide (CuS) as a novel signal probe was successfully developed for ultrasensitive and selective determination of sulfathiazole (STZ). The reduction signals of Cu2+ produced in the process of electron transfer of CuS containing large amounts of Cu2+ are easy to be captured, which provide high electrochemical signals. Moreover, gold nanoparticles@covalent organic framework with excellent conductivity was introduced on the electrode surface for signal amplification and facilitating electron transfer processes of CuS. Under optimized testing conditions, the proposed sensor offered a linear DPV response to STZ over a very wide concentration range (1.0 × 10-4 to 1.0 × 10-11 mol L-1), with a limit of detection of 4.3 × 10-12 mol L-1. Fodder and mutton samples spiked with STZ were analyzed using this sensor, and the satisfactory recoveries ranging from 83.0% to 107.2% were obtained. In addition, the proposed sensor was used to determine the concentration of STZ in chicken liver and pork liver, with quantification results being near identical to those determined by high-performance liquid chromatography.


Assuntos
Cobre/química , Eletroquímica/instrumentação , Ouro/química , Limite de Detecção , Nanopartículas Metálicas/química , Impressão Molecular , Sulfatiazóis/análise , Eletrodos , Sulfatiazóis/química
17.
Proc Natl Acad Sci U S A ; 117(31): 18470-18476, 2020 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-32690682

RESUMO

Lipid membrane fusion is an essential process for a number of critical biological functions. The overall process is thermodynamically favorable but faces multiple kinetic barriers along the way. Inspired by nature's engineered proteins such as SNAP receptor [soluble N-ethylmale-imide-sensitive factor-attachment protein receptor (SNARE)] complexes or viral fusogenic proteins that actively promote the development of membrane proximity, nucleation of a stalk, and triggered expansion of the fusion pore, here we introduce a synthetic fusogen that can modulate membrane fusion and equivalently prime lipid membranes for calcium-triggered fusion. Our fusogen consists of a gold nanoparticle functionalized with an amphiphilic monolayer of alkanethiol ligands that had previously been shown to fuse with lipid bilayers. While previous efforts to develop synthetic fusogens have only replicated the initial steps of the fusion cascade, we use molecular simulations and complementary experimental techniques to demonstrate that these nanoparticles can induce the formation of a lipid stalk and also drive its expansion into a fusion pore upon the addition of excess calcium. These results have important implications in general understanding of stimuli-triggered fusion and the development of synthetic fusogens for biomedical applications.


Assuntos
Cálcio/metabolismo , Membrana Celular/metabolismo , Ouro/química , Bicamadas Lipídicas/metabolismo , Nanopartículas Metálicas/química , Cálcio/química , Membrana Celular/química , Ouro/metabolismo , Humanos , Bicamadas Lipídicas/química , Fusão de Membrana , Simulação de Dinâmica Molecular , Proteínas SNARE/metabolismo , Análise Serial de Tecidos
18.
J Chromatogr A ; 1625: 461323, 2020 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-32709353

RESUMO

An overarching theory of chromatography capable of modeling all analyte-stationary phase interactions would enable predictive design of pharmaceutically relevant separations. The stochastic theory of chromatography has been postulated as a suitable basis to achieve this goal. Here, we implement Dondi and Cavazzini's Monte Carlo framework that utilizes experimentally accessible single molecule kinetics and use it to correlate heterogenous adsorption statistics at the stationary phase to shifts in asymmetry. The contributions cannot be captured or modeled through ensemble chemometrics. Simulations reveal that peak asymmetry scales non-linearly with longer analyte-stationary phase interactions and migrates towards symmetry across the column length, even without column overloading.


Assuntos
Cromatografia/métodos , Simulação por Computador , Método de Monte Carlo , Adsorção , Ouro/química , Cinética , Tamanho da Partícula , Processos Estocásticos
19.
Chemosphere ; 260: 127615, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32683014

RESUMO

In this work, a N-containing polymer was successfully synthesized by one-step treatment with 3-amine-1,2,4-triazole ligands and Zn(II) using the thermal solvent method, and employed to recover Au(III) from water. The adsorption kinetics was comprehensively studied through kinetics models including pseudo-first-order model, pseudo-second-order model, moving boundary model and Weber-Morris model. It is found that the overall adsorption rate was determined by chemical adsorption, and the rate-limiting step of diffusion steps is film diffusion. Rising temperature can improve the adsorption rate significantly, making the adsorption equilibrium time be reduced from 6 h at 298 K to 2 h at 318 K. The adsorption isotherm can be described well by Sips model, indicating it is a heterogeneous adsorption. The material shows high adsorption capacity towards Au(III) up to 1073 mg/g. It shows strong affinity towards Au(III) in the mixture solutions containing Au(III), Cu(II), Zn(II), Co(II), Cd(II), Pb(II) and Ni(II) ions. The material can be easily and completely desorbed by thiourea solution and still maintains its adsorption performance only with a slight decrease after three cycles. Combined with studies on pH influence, adsorption kinetics, adsorption isotherm and XPS analysis, it can be concluded that the adsorption mechanism could be attributed to electrostatic interaction, the coordination of the Zn-OH and -C-N/-CN- with Au(III), and partial reduction of Au(III) to Au(I) by -NH group on the polymer. The N-containing polymer is an excellent candidate for Au(III) recovery efficiently and selectively from aqueous solution.


Assuntos
Ouro/química , Poluentes Químicos da Água/química , Adsorção , Quitosana , Difusão , Concentração de Íons de Hidrogênio , Íons , Cinética , Polímeros , Temperatura , Água
20.
J Chromatogr A ; 1624: 461215, 2020 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-32540065

RESUMO

A method for the preparation of an on-column ESI emitter used as the sheathless interface for coupling capillary electrophoresis (CE) with mass spectrometry (MS) was developed. The emitter was directly fabricated at the outlet end of the separation capillary which was etched with HF solution to a symmetrical tip. The tip was covered with a small piece of gold foil which was fixed by epoxy resin glue for electrical contact. Such a prepared ESI emitter can produce a stable ESI signal over the wide range of flow rate from 50 nL/min to 800 nL/min. The performance of the CE-MS with the sheathless interface was evaluated by using the separation of four alkaloids. It was found that the strong electroosmotic flow produced by the multiple polyelectrolyte coating on the capillary is necessary for maintaining a stable MS signal. Effect of the running buffer composition, concentration and the CE separation voltages on the ESI signal strength were investigated. The absolute detection limits for the alkaloids was determined as fmol level. Moreover, the CE-MS was applied for the analyses of trypsin digestion of cytochrome C and small molecular organic anions. The emitter performed very stable with a lifetime of at least 180 h.


Assuntos
Ouro/química , Dióxido de Silício/química , Espectrometria de Massas por Ionização por Electrospray/métodos , Alcaloides/análise , Eletroforese Capilar , Limite de Detecção , Polieletrólitos/química
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