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1.
ACS Sens ; 9(6): 3009-3016, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38836608

RESUMO

Immune checkpoint inhibitors (ICIs) targeting programmed cell death ligand 1 (PD-L1), or its receptor, PD-1 have improved survival in patients with non-small-cell lung cancer (NSCLC). Assessment of PD-L1 expression requires tissue biopsy or fine needle aspiration that are currently used to identify patients most likely to respond to single agent anti-PD-1/PD-L1 therapy. However, obtaining sufficient tissue to generate a PD-L1 tissue proportion score (TPS) ≥ 50% using immunohistochemistry remains a challenge that potentially may be overcome by liquid biopsies. This study utilized a mesoporous gold sensor (MGS) assay to examine the phosphorylation status of PD-L1 in plasma extracellular vesicles (EV pPD-L1) and PD-L1 levels in plasma from NSCLC patient samples and their association with tumor PD-L1 TPS. The 3-dimensional mesoporous network of the electrodes provides a large surface area, high signal-to-noise ratio, and a superior electro-conductive framework, thereby significantly improving the detection sensitivity of PD-L1 nanosensing. Test (n = 20) (Pearson's r = 0.99) and validation (n = 45) (Pearson's r = 0.99) cohorts show that EV pPD-L1 status correlates linearly with the tumor PD-L1 TPS assessed by immunohistochemistry irrespective of the tumor stage, with 64% of patients overall showing detectable EV pPD-L1 levels in plasma. In contrast to the EV pPD-L1 results, plasma PD-L1 levels did not correlate with the tumor PD-L1 TPS score or EV pPD-L1 levels. These data demonstrate that EV pPD-L1 levels may be used to select patients for appropriate PD-1 and PD-L1 ICI therapy regimens in early, locally advanced, and advanced NSCLC and should be tested further in randomized controlled trials. Most importantly, the assay used has a less than 24h turnaround time, facilitating adoption of the test into the routine diagnostic evaluation of patients prior to therapy.


Assuntos
Antígeno B7-H1 , Carcinoma Pulmonar de Células não Pequenas , Vesículas Extracelulares , Ouro , Neoplasias Pulmonares , Humanos , Antígeno B7-H1/metabolismo , Antígeno B7-H1/sangue , Vesículas Extracelulares/química , Vesículas Extracelulares/metabolismo , Ouro/química , Neoplasias Pulmonares/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Fosforilação , Porosidade , Técnicas Biossensoriais/métodos , Pessoa de Meia-Idade , Masculino , Feminino
2.
Biosens Bioelectron ; 249: 115984, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38219464

RESUMO

Immune checkpoint proteins (ICPs) play a major role in a patient's immune response against cancer. Tumour cells usually express those proteins to communicate with immune cells as a process of escaping the anti-cancer immune response. Detecting the major functional immune checkpoint proteins present on cancer cells (such as circulating tumor cells or CTCs) and examining the heterogeneity in their expression at the single-cell level could play a crucial role in both cancer diagnosis and the monitoring of therapy. In this study, we develop a mesoporous gold biosensor to precisely assess ICP heterogeneity in individual cancer cells within a lung cancer model. The platform utilizes a nanostructured mesoporous gold surface to capture CTCs and a Surface Enhanced Raman Scattering (SERS) readout to identify and monitor the expression of key ICP proteins (PD-L1, B7H4, CD276, CD80) in lung cancer cells. The homogeneous and abundant pores in mesoporous 3D gold nanostructures enable increased antibody loading on-chip and an enhanced SERS signal, which are key to our single cell capture, and accurate analysis of ICPs in cancer cells with high sensitivity. Our lung cancer cell line model data showed that our method can detect single cells and analyse the expression of four lung cancer associated ICPs on individual cell surfaces during treatment. To show the potential of our mesoporous gold biosensor in analysing clinical samples, we tested 9 longitudinal Peripheral Blood Mononuclear Cells (PBMC) samples from lung cancer patient before and after therapy. Our mesoporous biosensor successfully captured single CTCs and found that the expression of ICPs in CTCs is highly heterogeneous in both pre-treatment and treated PBMC samples isolated from lung cancer patient blood. We suggest that our findings will help clinicians in selecting the most appropriate therapy for patients.


Assuntos
Técnicas Biossensoriais , Neoplasias Pulmonares , Células Neoplásicas Circulantes , Humanos , Proteínas de Checkpoint Imunológico , Leucócitos Mononucleares , Ouro , Células Neoplásicas Circulantes/patologia , Antígenos B7
3.
ACS Nano ; 17(4): 3346-3357, 2023 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-36744876

RESUMO

Construction of a well-defined mesoporous nanostructure is crucial for applying nonnoble metals in catalysis and biomedicine owing to their highly exposed active sites and accessible surfaces. However, it remains a great challenge to controllably synthesize superparamagnetic CoFe-based mesoporous nanospheres with tunable compositions and exposed large pores, which are sought for immobilization or adsorption of guest molecules for magnetic capture, isolation, preconcentration, and purification. Herein, a facile assembly strategy of a block copolymer was developed to fabricate a mesoporous CoFeB amorphous alloy with abundant metallic Co/Fe atoms, which served as an ideal scaffold for well-dispersed loading of Au nanoparticles (∼3.1 nm) via the galvanic replacement reaction. The prepared Au-CoFeB possessed high saturation magnetization as well as uniform and large open mesopores (∼12.5 nm), which provided ample accessibility to biomolecules, such as nucleic acids, enzymes, proteins, and antibodies. Through this distinctive combination of superparamagnetism (CoFeB) and biofavorability (Au), the resulting Au-CoFeB was employed as a dispersible nanovehicle for the direct capture and isolation of p53 autoantibody from serum samples. Highly sensitive detection of the autoantibody was achieved with a limit of detection of 0.006 U/mL, which was 50 times lower than that of the conventional p53-ELISA kit-based detection system. Our assay is capable of quantifying differential expression patterns for detecting p53 autoantibodies in ovarian cancer patients. This assay provides a rapid, inexpensive, and portable platform with the potential to detect a wide range of clinically relevant protein biomarkers.


Assuntos
Nanopartículas Metálicas , Feminino , Humanos , Nanopartículas Metálicas/química , Autoanticorpos , Ouro/química , Proteína Supressora de Tumor p53 , Nanopartículas Magnéticas de Óxido de Ferro
4.
Environ Res ; 190: 109976, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32750555

RESUMO

Fast pyrolysis of lignin can obtain valuable products such as bio-oil, bio-chemical, syngas, and biochar. In this study, two types of lignin known as brown solid from the byproduct of cellulosic ethanol fermentation and commercial dealkaline lignin from the papermaking process were used for pyrolysis in a 3-L batch reactor at 300-450 °C. The product composition in the liquid and gas phases were analyzed by using gas chromatography-mass spectrometry/Flame-ionization detector/thermal conductivity detector (GC-MS/FID/TCD). Increasing the N2 flow rate to 150 mL/min was sufficient to increase the production of bio-oil/bio-organics up to 15% for brown solid pyrolysis. In contrast, the biochemical production during dealkaline lignin pyrolysis was not sensitive to the change of the N2 flow rate. The amount of biochar produced in the pyrolysis (~60%) slightly changed at various pyrolysis temperature and gas flow rate, which could be due to the relatively low pyrolysis temperature that was insufficient to decompose the lignin. The GC-MS analysis also revealed that C7-C8 compounds, which represented the phenolic compounds, were the most abundant in the liquid products. Kinetic models of the pyrolysis were established based on the thermogravimetric analysis.


Assuntos
Lignina , Pirólise , Biocombustíveis , Cromatografia Gasosa-Espectrometria de Massas , Temperatura Alta , Fenóis , Temperatura
5.
Analyst ; 145(20): 6639-6648, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-32797121

RESUMO

Protein phosphorylation is a post-translational modification of kinase proteins that changes a protein's conformation to regulate crucial biological functions. However, the phosphorylation of protein is significantly altered during cancer progression which triggers abnormal cellular pathways and this phosphorylation can serve as an emergent diagnostic and prognostic biomarker for cancer. Herein, we develop a nanostructured mesoporous gold electrode (NMGE)-based biosensor that enables a highly sensitive detection of protein phosphorylation with electrochemical signal amplification. The biosensor comprises nanostructured mesoporous gold electrodes whose electro-conductive framework is superior to that of the nonporous electrodes. We characterize our developed nano/mesoporous gold electrode with various electrochemical methods in the presence of the [Fe(CN)6]3-/4- redox system. We find that the mesoporous gold electrode catalyzes both the oxidation and reduction processes of the [Fe(CN)6]3-/4- system and generates a current signal that is 3 times higher than that of the nonporous gold electrode. This superior signal transduction of our nano/mesoporous gold electrode is enabled through a pore-induced (i) high electrochemically active surface area and (ii) reduced impedance with a high signal to noise ratio. The assay utilizes direct adsorption of an immunoprecipitated purified BRAF protein towards the mesoporous gold electrode and thus avoids the cumbersome sensor surface functionalization. Our developed biosensor detects the phosphorylated BRAF protein with a 2.5-fold increase in sensitivity and an ≈10-fold increase in the limit of detection (LOD) in comparison with the nonporous gold electrodes. The assay also works on a wide dynamic range from 0.5 to 20 ng µL-1 of the protein which further shows its potential for clinical application. We envisage that this nanostructured mesoporous gold biosensor will be of high interest for clinical application.


Assuntos
Técnicas Biossensoriais , Neoplasias , Técnicas Eletroquímicas , Eletrodos , Ouro , Humanos , Limite de Detecção , Fosforilação
6.
Nanoscale ; 12(29): 15611-15619, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32678409

RESUMO

Constructing heterostructures with advanced architectures is an effective strategy for enhancing the crystallinity and functional performance of covalent organic frameworks (COFs). Herein, a novel core-shell heterostructure integrating a metal-organic framework (MOF)-derived graphitic carbon core (GC) and a well-arranged COF shell, termed MOF-GC@COF, is reported. ZIF-67 dodecahedra are first chemically etched with a weak organic acid and further converted to MOF-GC via thermal pyrolysis. In the subsequent step, ß-ketoenamine-linked COF nanofibers are vertically assembled on the surface of the MOF-GC cores to generate the MOF-GC@COF heterostructure. As a proof-of-concept application, the as-prepared MOF-GC@COF heterostructure is used as an effective quartz crystal microbalance (QCM) sensor for the adsorption of formaldehyde. Benefiting from the synergistic effect of the hybrid composition and the advantages of the core-shell heterostructure, the newly prepared MOF-GC@COF heterostructure exhibits excellent sensing performance toward formaldehyde with rapid adsorption kinetics, high sensitivity, and superior selectivity.

7.
ACS Nano ; 14(4): 4141-4152, 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32191030

RESUMO

Mesoporous metal sulfide hybrid (meso-MoS2/CoMo2S4) materials via a soft-templating approach using diblock copolymer polystyrene-block-poly(acrylic acid) micelles are reported. The formation of the meso-MoS2/CoMo2S4 heterostructures is based on the sophisticated coassembly of dithiooxamide and metal precursors (i.e., Co2+, PMo12), which are subsequently annealed in nitrogen atmosphere to generate the mesoporous material. Decomposing the polymer leaves behind mesopores throughout the spherical MoS2/CoMo2S4 hybrid particles, generating numerous electrochemical active sites in a network of pores that enable faster charge transfer and mass/gas diffusion that enhance the electrocatalytic performance of MoS2/CoMo2S4. Doping the spherical meso-MoS2/CoMo2S4 heterostructures with iron improves the electronic properties of the hybrid meso-Fe-MoS2/CoMo2S4 material and consequently results in its superior electrochemical activities for both hydrogen evolution reaction and oxygen evolution reaction.

8.
Chem Soc Rev ; 48(24): 5717-5751, 2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31720618

RESUMO

The detection of clinically relevant disease-specific biomolecules, including nucleic acids, circulating tumor cells, proteins, antibodies, and extracellular vesicles, has been indispensable to understand their functions in disease diagnosis and prognosis. Therefore, a biosensor for the robust, ultrasensitive, and selective detection of these low-abundant biomolecules in body fluids (blood, urine, and saliva) is emerging in current clinical research. In recent years, nanomaterials, especially superparamagnetic nanomaterials, have played essential roles in biosensing due to their intrinsic magnetic, electrochemical, and optical properties. However, engineered multicomponent magnetic nanoparticle-based current biosensors that offer the advantages of excellent stability in a complex biomatrix; easy and alterable biorecognition of ligands, antibodies, and receptor molecules; and unified point-of-care integration have yet to be achieved. This review introduces the recent advances in superparamagnetic nanostructures for electrochemical and optical biosensing for disease-specific biomarkers. This review emphasizes the synthesis, biofunctionalization, and intrinsic properties of nanomaterials essential for robust, ultrasensitive biosensing. With a particular emphasis on nanostructure-based electrochemical and optical detection of disease-specific biomarkers such as nucleic acids (DNA and RNA), proteins, autoantibodies, and cells, this review also chronicles the needs and challenges of nanoarchitecture-based detection. These summaries provide further insights for researchers to inspire their future work on the development of nanostructures for integrating into biosensing and devices for a broad field of applications in analytical sensing and in clinic.


Assuntos
Técnicas Biossensoriais/métodos , Nanopartículas de Magnetita/química , Animais , Anticorpos/análise , Biomarcadores/análise , Técnicas Biossensoriais/instrumentação , Técnicas Eletroquímicas/instrumentação , Técnicas Eletroquímicas/métodos , Desenho de Equipamento , Humanos , Nanopartículas de Magnetita/ultraestrutura , Nanotecnologia/métodos , Ácidos Nucleicos/análise , Proteínas/análise
9.
J Mater Chem B ; 7(35): 5412-5422, 2019 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-31414694

RESUMO

Nanozymes (nanoparticles with enzyme-like properties) have attracted considerable attention in recent years owing to their intrinsic enzyme-like properties and broad application in the fields of ELISA based immunoassay and biosensing. Herein, we systematically investigate the influence of crystal phases (γ-Fe2O3 and α-Fe2O3) of mesoporous iron oxide (IO) on their peroxidase mimetic activity. In addition, we have also demonstrated the applicability of these mesoporous IOs as nanozymes for detecting the glucose biomarker with a limit of detection (LOD) of 0.9 µM. Mesoporous γ-Fe2O3 shows high nanozyme activities (and magnetism) toward the catalytic oxidation of chromogenic substances, such as 3,3',5,5'-tetramethylbenzidine (TMB) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)-ABTS, as well as for the colourimetric detection of glucose, compared to that of α-Fe2O3. We believe that this in-depth study of crystal structure based nanozyme activity will guide designing highly effective nanozymes based on iron oxide nanostructures for chemical sensing, biosensing and environmental remediation.


Assuntos
Biomimética , Técnicas Biossensoriais , Compostos Férricos/química , Glucose/análise , Nanopartículas/química , Oxirredução
10.
Anal Chem ; 91(6): 3827-3834, 2019 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-30735354

RESUMO

Most of the current exosome-analysis strategies are time-consuming and largely dependent on commercial extraction kit-based preisolation step, which requires extensive sample manipulations, costly isolation kits, reagents, tedious procedures, and sophisticated equipment and is prone to bias/artifacts. Herein we introduce a simple method for direct isolation and subsequent detection of a specific population of exosomes using an engineered superparamagnetic material with multifunctional properties, namely, gold-loaded ferric oxide nanocubes (Au-NPFe2O3NC). In this method, the Au-NPFe2O3NC were initially functionalized with a generic tetraspanin (exosomes-associated) antibody (i.e., CD63) and dispersed in sample fluids where they work as "dispersible nanocarriers" to capture the bulk population of exosomes. After magnetic collection and purification, Au-NPFe2O3NC-bound exosomes were transferred to the tissue-specific, antibody-modified, screen-printed electrode. As a proof of principle, we used a specific placental marker, placenta alkaline phosphatase (PLAP), to detect exosomes secreted from placental cells. The peroxidase-like activity of Au-NPFe2O3NC was then used to accomplish an enzyme-linked immunosorbent assay (ELISA)-based sensing protocol for naked-eye observation along with UV-visible and electrochemical detection of PLAP-specific exosomes present in placental cell-conditioned media. We demonstrated excellent agreement in analytical performance for the detection of placental cell-derived exosomes (i.e., linear dynamic range, 103-107 exosomes/mL; limit of detection, 103 exosomes/mL; relative standard deviation (%RSD) of <5.5% for n = 3) using with and without commercial "total exosome isolation kit"-based preisolation step. We envisage that this highly sensitive, rapid, and inexpensive assay could be useful in quantifying specific populations of exosomes for various clinical applications, focusing on pregnancy complications.


Assuntos
Fosfatase Alcalina/metabolismo , Técnicas Biossensoriais/métodos , Exossomos/metabolismo , Compostos Férricos/química , Ouro/química , Limite de Detecção , Nanoporos , Linhagem Celular Tumoral , Feminino , Humanos , Placenta/enzimologia , Gravidez
11.
RSC Adv ; 9(31): 17717-17725, 2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-35520545

RESUMO

It has been suggested that electromagnetic fields could be used to differentiate neurons in culture but how to do this is not clear. We investigated the effect of external magnetic fields (DC and AC MF) on neuronal viability, differentiation, and neurite outgrowth of human SH-SY5Y neuroblastoma cells in vitro. A strong low frequency DC MF or a weak AC MF improved retinoic acid-mediated neuronal differentiation and increased neurite length, without any adverse effects on neuronal viability. Even in the absence of the conventional differentiation factor, retinoic acid, DC and AC MF promoted neurite outgrowth. No significant negative effect on cell viability was observed after MF exposure and the DC MF had greater effects on neurite length and branch number than AC MF. Thus, we have identified a novel, simple and cost-effective method that is easy to set up in any cell culture laboratory that can be used to efficiently differentiate neuronal-like cells, using a DC MF without the need for expensive reagents. This research provides a fresh approach to promote neurite outgrowth in a commonly used neuronal-like cell line model and may be applicable to neural stem cells or primary neurons.

12.
Chem Commun (Camb) ; 54(61): 8514-8517, 2018 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-30009299

RESUMO

In this work, we fabricate a highly effective catalyst for carbon monoxide oxidation based on gold-loaded mesoporous maghemite nanoflakes which exhibit nearly 100% CO conversion and a very high specific activity of 8.41 molCO gAu-1 h-1 at room temperature. Such excellent catalytic activity is promoted by the synergistic cooperation of their high surface area, large pore volume, and mesoporous structure.

13.
Nanoscale ; 10(10): 4779-4785, 2018 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-29469140

RESUMO

Herein, we report the synthesis of gold (Au)-loaded mesoporous iron oxide (Fe2O3) as a catalyst for both CO and NH3 oxidation. The mesoporous Fe2O3 is firstly prepared using polymeric micelles made of an asymmetric triblock copolymer poly(styrene-b-acrylic acid-b-ethylene glycol) (PS-b-PAA-b-PEG). Owing to its unique porous structure and large surface area (87.0 m2 g-1), the as-prepared mesoporous Fe2O3 can be loaded with a considerably higher amount of Au nanoparticles (Au NPs) (7.9 wt%) compared to the commercial Fe2O3 powder (0.8 wt%). Following the Au loading, the mesoporous Fe2O3 structure is still well-retained and Au NPs with varying sizes of 3-10 nm are dispersed throughout the mesoporous support. When evaluated for CO oxidation, the Au-loaded mesoporous Fe2O3 catalyst shows up to 20% higher CO conversion efficiency compared to the commercial Au/Fe2O3 catalyst, especially at lower temperatures (25-150 °C), suggesting the promising potential of this catalyst for low-temperature CO oxidation. Furthermore, the Au-loaded mesoporous Fe2O3 catalyst also displays a higher catalytic activity for NH3 oxidation with a respectable conversion efficiency of 37.4% compared to the commercial Au/Fe2O3 catalyst (15.6%) at 200 °C. The significant enhancement in the catalytic performance of the Au-loaded mesoporous Fe2O3 catalyst for both CO and NH3 oxidation may be attributed to the improved dispersion of the Au NPs and enhanced diffusivity of the reactant molecules due to the presence of mesopores and a higher oxygen activation rate contributed by the increased number of active sites, respectively.

14.
ACS Appl Mater Interfaces ; 10(1): 1039-1049, 2018 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-29185699

RESUMO

Herein, we report the soft-templated preparation of mesoporous iron oxide using an asymmetric poly(styrene-b-acrylic acid-b-ethylene glycol) (PS-b-PAA-b-PEG) triblock copolymer. This polymer forms a micelle consisting of a PS core, a PAA shell, and a PEG corona in aqueous solutions, which can serve as a soft template. The mesoporous iron oxide obtained at an optimized calcination temperature of 400 °C exhibited an average pore diameter of 39 nm, with large specific surface area and pore volume of 86.9 m2 g-1 and 0.218 cm3 g-1, respectively. The as-prepared mesoporous iron oxide materials showed intrinsic peroxidase-like activities toward the catalytic oxidation of 3,3',5,5'-tertamethylbenzidine (TMB) in the presence of hydrogen peroxide (H2O2). This mimetic feature was further exploited to develop a simple colorimetric (naked-eye) and electrochemical assay for the detection of glucose. Both our colorimetric (naked-eye and UV-vis) and electrochemical assays estimated the glucose concentration to be in the linear range from 1.0 µM to 100 µM with a detection limit of 1.0 µM. We envisage that our integrated detection platform for H2O2 and glucose will find a wide range of applications in developing various biosensors in the field of personalized medicine, food-safety detection, environmental-pollution control, and agro-biotechnology.


Assuntos
Colorimetria , Etilenoglicóis , Compostos Férricos , Glucose , Peróxido de Hidrogênio , Micelas , Estirenos
15.
Small ; 14(6)2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29282861

RESUMO

Exosomes are nanoscale (≈30-150 nm) extracellular vesicles of endocytic origin that are shed by most types of cells and circulate in bodily fluids. Exosomes carry a specific composition of proteins, lipids, RNA, and DNA and can work as cargo to transfer this information to recipient cells. Recent studies on exosomes have shown that they play an important role in various biological processes, such as intercellular signaling, coagulation, inflammation, and cellular homeostasis. These functional roles are attributed to their ability to transfer RNA, proteins, enzymes, and lipids, thereby affecting the physiological and pathological conditions in various diseases, including cancer and neurodegenerative, infectious, and autoimmune diseases (e.g., cancer initiation, progression, and metastasis). Due to these unique characteristics, exosomes are considered promising biomarkers for the diagnosis and prognosis of various diseases via noninvasive or minimally invasive procedures. Over the last decade, a plethora of methodologies have been developed for analyzing disease-specific exosomes using optical and nonoptical tools. Here, the major biological functions, significance, and potential role of exosomes as biomarkers and therapeutics are discussed. Furthermore, an overview of the most commonly used techniques for exosome analysis, highlighting the major technical challenges and limitations of existing techniques, is presented.

16.
J Mater Chem B ; 6(29): 4783-4791, 2018 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32254305

RESUMO

Nanomaterials (nanozymes) with peroxidase-mimetic activity have been widely used in biosensing platforms as low-cost, relatively stable and prevailing alternatives to natural enzymes. Herein, we report on the synthesis and application of the peroxidase-mimetic activity of mesoporous iron oxide (MIO) for the detection of global DNA methylation in colorectal cancer cell lines. The target DNA was extracted and denatured to get ssDNA followed by direct adsorption onto the surface of a bare screen-printed gold electrode (SPGE). A 5-methylcytosine antibody (5mC) functionalized nanomaterial (MIO-5mC) was then used to recognise the methylcytosine groups present on the SPGE. The MIO-5mC conjugates catalyse the TMB solution in the presence of hydrogen peroxide to give the colorimetric (i.e., naked-eye observation) and electrochemical detection of DNA methylation. The assay could successfully detect as low as 10% difference in the global DNA methylation level in synthetic samples and cell lines with good reproducibility and specificity (%RSD = <5%, for n = 3). This strategy avoids the use of natural enzyme horseradish peroxidase (HRP), traditional PCR based amplification and bisulfite treatment steps that are generally used in many conventional DNA methylation assays. We envisage that our assay could be a low-cost platform with great potential for genome-wide DNA methylation analysis in point-of-care applications.

17.
ACS Appl Mater Interfaces ; 9(44): 38737-38744, 2017 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-29082737

RESUMO

Metal-organic frameworks (MOFs) with high porosity and a regular porous structure have emerged as a promising electrode material for supercapacitors, but their poor electrical conductivity limits their utilization efficiency and capacitive performance. To increase the overall electrical conductivity as well as the efficiency of MOF particles, three-dimensional networked MOFs are developed via using preprepared conductive polypyrrole (PPy) tubes as the support for in situ growth of MOF particles. As a result, the highly conductive PPy tubes that run through the MOF particles not only increase the electron transfer between MOF particles and maintain the high effective porosity of the MOFs but also endow the MOFs with flexibility. Promoted by such elaborately designed MOF-PPy networks, the specific capacitance of MOF particles has been increased from 99.2 F g-1 for pristine zeolitic imidazolate framework (ZIF)-67 to 597.6 F g-1 for ZIF-PPy networks, indicating the importance of the design of the ZIF-PPy continuous microstructure. Furthermore, a flexible supercapacitor device based on ZIF-PPy networks shows an outstanding areal capacitance of 225.8 mF cm-2, which is far above other MOFs-based supercapacitors reported up to date, confirming the significance of in situ synthetic chemistry as well as the importance of hybrid materials on the nanoscale.

18.
Anal Chem ; 89(20): 11005-11013, 2017 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-28892622

RESUMO

The enzyme-mimicking activity of iron oxide based nanostructures has provided a significant advantage in developing advanced molecular sensors for biomedical and environmental applications. Herein, we introduce the horseradish peroxidase (HRP)-like activity of gold-loaded nanoporous ferric oxide nanocubes (Au-NPFe2O3NC) for the development of a molecular sensor with enhanced electrocatalytic and colorimetric (naked eye) detection of autoantibodies. The results showed that Au-NPFe2O3NC exhibits enhanced peroxidase-like activity toward the catalytic oxidation of 3,3',5,5'-tertamethylbenzidine (TMB) in the presence of H2O2 at room temperature (25 °C) and follows the typical Michaelis-Menten kinetics. The autoantibody sensor based on this intrinsic property of Au-NPFe2O3NC resulted in excellent detection sensitivity [limit of detection (LOD) = 0.08 U/mL] and reproducibility [percent relative standard deviation (% RSD) = <5% for n = 3] for analyzing p53-specific autoantibodies using electrochemical and colorimetric (naked eye) readouts. The clinical applicability of the sensor has been tested in detecting p53-specific autoantibody in plasma obtained from patients with epithelial ovarian cancer high-grade serous subtype (EOCHGS, number of samples = 2) and controls (benign, number of samples = 2). As Au-NPFe2O3NC possess high peroxidase-like activity for the oxidation of TMB in the presence of H2O2 [TMB is a common chromogenic substrate for HRP in enzyme-linked immunosorbent assays (ELISAs)], we envisage that our assay could find a wide range of application in developing ELISA-based sensing approaches in the fields of medicine (i.e., detection of other biomarkers the same as p53 autoantibody), biotechnology, and environmental sciences.


Assuntos
Autoanticorpos/sangue , Materiais Biocompatíveis/química , Colorimetria/métodos , Compostos Férricos/química , Ouro/química , Nanoestruturas/química , Autoanticorpos/análise , Materiais Biocompatíveis/metabolismo , Catálise , Técnicas Eletroquímicas , Feminino , Humanos , Peróxido de Hidrogênio/química , Cinética , Limite de Detecção , Nanoporos , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Oxirredução , Peroxidases/metabolismo , Reprodutibilidade dos Testes , Proteína Supressora de Tumor p53/imunologia
19.
Chem Commun (Camb) ; 53(58): 8231-8234, 2017 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-28681881

RESUMO

This paper reports the development of a nonenzymatic, amplification-free, and sensitive platform for the detection of microRNA based on a new class of electrocatalytically active superparamagnetic gold-loaded nanoporous iron oxide nanocubes (Au@NPFe2O3NC). The assay showed an excellent detection sensitivity down to 100 fM and specificity towards the analysis of miR-21 in cell lines and tissue samples derived from patients with oesophageal squamous-cell carcinoma (ESCC).


Assuntos
Técnicas Biossensoriais , Técnicas Eletroquímicas , Ouro/química , Nanopartículas de Magnetita/química , MicroRNAs/análise , Nanoporos , Catálise , Linhagem Celular Tumoral , Humanos , MicroRNAs/síntese química , Tamanho da Partícula , Propriedades de Superfície
20.
ACS Biomater Sci Eng ; 3(10): 2366-2374, 2017 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33445294

RESUMO

Chemotherapy of bladder cancer has limited efficacy because of the short retention time of drugs in the bladder during therapy. In this research, nanoparticles (NPs) with a new core/shell/corona nanostructure have been synthesized, consisting of iron oxide (Fe3O4) as the core to providing magnetic properties, drug (doxorubicin) loaded calcium phosphate (CaP) as the shell for pH-responsive release, and arginylglycylaspartic acid (RGD)-containing peptide functionalized alginate as the corona for cell targeting (with the composite denoted as RGD-Fe3O4/CaP/Alg NPs). We have optimized the reaction conditions to obtain RGD-Fe3O4/CaP/Alg NPs with high biocompatibility and suitable particle size, surface functionality, and drug loading/release behavior. The results indicate that the RGD-Fe3O4/CaP/Alg NPs exhibit enhanced chemotherapy efficacy toward T24 bladder cancer cells, owing to successful magnetic guidance, pH-responsive release, and improved cellular uptake, which give these NPs great potential as therapeutic agents for future in vivo drug delivery systems.

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