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1.
Pharm Res ; 37(10): 196, 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32944844

RESUMO

PURPOSE: Hypoxia-inducible factor (HIF) is one of the critical components of the tumor microenvironment that is involved in tumor development. HIF-1α functionally and physically interacts with CDK1, 2, and 5 and stimulates the cell cycle progression and Cyclin-Dependent Kinase (CDK) expression. Therefore, hypoxic tumor microenvironment and CDK overexpression lead to increased cell cycle progression and tumor expansion. Therefore, we decided to suppress cancer cell expansion by blocking HIF-1α and CDK molecules. METHODS: In the present study, we used the carboxylated graphene oxide (CGO) conjugated with trimethyl chitosan (TMC) and hyaluronate (HA) nanoparticles (NPs) loaded with HIF-1α-siRNA and Dinaciclib, the CDK inhibitor, for silencing HIF-1α and blockade of CDKs in CD44-expressing cancer cells and evaluated the impact of combination therapy on proliferation, metastasis, apoptosis, and tumor growth. RESULTS: The results indicated that the manufactured NPs had conceivable physicochemical properties, high cellular uptake, and low toxicity. Moreover, combination therapy of cancer cells using CGO-TMC-HA NPs loaded with HIF-1α siRNA and Dinaciclib (SCH 727965) significantly suppressed the CDKs/HIF-1α and consequently, decreased the proliferation, migration, angiogenesis, and colony formation in tumor cells. CONCLUSIONS: These results indicate the ability of CGO-TMC-HA NPs for dual drug/gene delivery in cancer treatment. Furthermore, the simultaneous inhibition of CDKs/HIF-1α can be considered as a novel anti-cancer treatment strategy; however, further research is needed to confirm this treatment in vivo. Graphical Abstract The suppression of HIF-1α and CDKs inhibits cancer growth. HIF-1α is overexpressed by the cells present in the tumor microenvironment. The hypoxic environment elevates mitochondrial ROS production and increases p38 MAP kinase, JAK/STAT, ERK, JNK, and Akt/PI3K signaling, resulting in cyclin accumulation and aberrant cell cycle progression. Furthermore, the overexpression of HIF-1α/CDK results in increased expression of genes such as BCL2, Bcl-xl, Ki-67, TGFß, VEGF, FGF, MMP2, MMP9, and, HIF-1α and consequently raise the survival, proliferation, angiogenesis, metastasis, and invasion of tumor cells. In conclusion, HIF-1α-siRNA/Dinaciclib-loaded CGO-TMC-HA NPs can inhibit the tumor expansion by blockage of CDKs and HIF-1α (JAK: Janus kinase, STAT: Signal transducer and activator of transcription, MAPK: mitogen-activated protein kinase, ERK: extracellular signal-regulated kinase, JNK: c-Jun N-terminal kinase, PI3K: phosphatidylinositol 3-kinase).


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Neoplasias Experimentais/terapia , Compostos de Piridínio/administração & dosagem , RNA Interferente Pequeno/administração & dosagem , Animais , Compostos Bicíclicos Heterocíclicos com Pontes/química , Compostos Bicíclicos Heterocíclicos com Pontes/farmacocinética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Quitosana/química , Grafite/química , Ácido Hialurônico/química , Camundongos , Nanopartículas/química , Neoplasias Experimentais/genética , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Compostos de Piridínio/química , Compostos de Piridínio/farmacocinética , RNA Interferente Pequeno/química , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/farmacocinética
2.
J Med Chem ; 63(8): 4107-4116, 2020 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-32202781

RESUMO

Bicycles are constrained bicyclic peptides that represent a promising binding modality for use in targeted drug conjugates. A phage display screen against EphA2, a receptor tyrosine kinase highly expressed in a number of solid tumors, identified a number of Bicycle families with low nanomolar affinity. A Bicycle toxin conjugate (BTC) was generated by derivatization of one of these Bicycles with the potent cytotoxin DM1 via a cleavable linker. This BTC demonstrated potent antitumor activity in vivo but was poorly tolerated, which was hypothesized to be the result of undesired liver uptake caused by poor physicochemical properties. Chemical optimization of a second Bicycle, guided by structural biology, provided a high affinity, metabolically stable Bicycle with improved physicochemical properties. A BTC incorporating this Bicycle also demonstrated potent antitumor activity and was very well tolerated when compared to the initial BTC. Phage display selection followed by chemical optimization of Bicycles can deliver potent drug conjugates with favorable pharmaceutical properties.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Citotoxinas/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Efrina-A2/antagonistas & inibidores , Sequência de Aminoácidos , Animais , Compostos Bicíclicos Heterocíclicos com Pontes/química , Compostos Bicíclicos Heterocíclicos com Pontes/metabolismo , Citotoxinas/química , Citotoxinas/metabolismo , Efrina-A2/metabolismo , Feminino , Humanos , Fígado/diagnóstico por imagem , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
3.
Chemistry ; 26(34): 7602-7608, 2020 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-32068310

RESUMO

In this study a bispidine ligand has been applied to the complexation of gallium(III) and radiolabelled with gallium-68 for the first time. Despite its 5-coordinate nature, the resulting complex is stable in serum for over two hours, demonstrating a ligand system well matched to the imaging window of gallium-68 positron emission tomography (PET). To show the versatility of the bispidine ligand and its potential use in PET, the bifunctional chelator was conjugated to a porphyrin, producing a PET/PDT-theranostic, which showed the same level of stability to serum as the non-conjugated gallium-68 complex. The PET/PDT complex killed >90 % of HT-29 cells upon light irradiation at 50 µm. This study shows bispidines have the versatility to be used as a ligand system for gallium-68 in PET.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes/química , Quelantes/química , Gálio/química , Porfirinas/química , Compostos Bicíclicos Heterocíclicos com Pontes/análise , Radioisótopos de Gálio , Humanos , Ligantes , Tomografia por Emissão de Pósitrons/métodos , Nanomedicina Teranóstica/métodos
4.
Molecules ; 25(2)2020 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-31940924

RESUMO

Over the past few decades, nanostructured conducting polymers have received great attention in several application fields, including biosensors, microelectronics, polymer batteries, actuators, energy conversion, and biological applications due to their excellent conductivity, stability, and ease of preparation. In the bioengineering application field, the conducting polymers were reported as excellent matrixes for the functionalization of various biological molecules and thus enhanced their performances as biosensors. In addition, combinations of metals or metal oxides nanostructures with conducting polymers result in enhancing the stability and sensitivity as the biosensing platform. Therefore, several methods have been reported for developing homogeneous metal/metal oxide nanostructures thin layer on the conducting polymer surfaces. This review will introduce the fabrications of different conducting polymers nanostructures and their composites with different shapes. We will exhibit the different techniques that can be used to develop conducting polymers nanostructures and to investigate their chemical, physical and topographical effects. Among the various biosensors, we will focus on conducting polymer-integrated electrochemical biosensors for monitoring important biological targets such as DNA, proteins, peptides, and other biological biomarkers, in addition to their applications as cell-based chips. Furthermore, the fabrication and applications of the molecularly imprinted polymer-based biosensors will be addressed in this review.


Assuntos
Técnicas Biossensoriais , DNA/análise , Técnicas Eletroquímicas , Glucose/análise , Peróxido de Hidrogênio/análise , Nanoestruturas/química , Proteínas/análise , Animais , Compostos Bicíclicos Heterocíclicos com Pontes/química , Condutividade Elétrica , Humanos , Metais/química , Impressão Molecular/métodos , Óxidos/química , Polímeros/química , Piridinas/química
5.
Chemistry ; 26(9): 1989-2001, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-31755596

RESUMO

Bifunctional chelators as parts of modular metal-based radiopharmaceuticals are responsible for stable complexation of the radiometal ion and for covalent linkage between the complex and the targeting vector. To avoid loss of complex stability, the bioconjugation strategy should not interfere with the radiometal chelation by occupying coordinating groups. The C9 position of the very stable CuII chelator 3,7-diazabicyclo[3.3.1]nonane (bispidine) is virtually predestined to introduce functional groups for facile bioconjugation as this functionalisation does not disturb the metal binding centre. We describe the preparation and characterisation of a set of novel bispidine derivatives equipped with suitable functional groups for diverse bioconjugation reactions, including common amine coupling strategies (bispidine-isothiocyanate) and the Cu-free strain-promoted alkyne-azide cycloaddition. We demonstrate their functionality and versatility in an exemplary way by conjugation to an antibody-based biomolecule and validate the obtained conjugate in vitro and in vivo.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes/química , Quelantes/química , Cobre/química , Compostos Radiofarmacêuticos/química , Animais , Compostos Bicíclicos Heterocíclicos com Pontes/síntese química , Linhagem Celular Tumoral , Cetuximab/química , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Reação de Cicloadição , Humanos , Camundongos , Microscopia de Fluorescência , Neoplasias/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/síntese química , Transplante Heterólogo
6.
Anal Chim Acta ; 1093: 93-105, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31735219

RESUMO

The detrimental effect of (NO2-) on environment, a sensitive and selective detection of nitrite (NO2-) ions with point-to-care device is need to be fabricated. Herein, we report the non-enzymatic nitrite sensor using a novel reduced graphene oxide/molybdenum disulfide/poly (3, 4-ethylene dioxythiophene) (rGO/MoS2/PEDOT) nanocomposite electrode. The rGO/MoS2/PEDOT nanocomposite was synthesized using facile and cost-effective hydrothermal and polymerization approaches. The characteristics of rGO-MoS2-PEDOT nanocomposite was investigated by X-ray diffraction (XRD), Fourier transform infrared (FT-IR), Raman, transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and Brunauer-Emmett-Teller (BET) analyses. The rGO-MoS2-PEDOT nanocomposite modified glassy carbon electrode (GCE) was directly used for electrocatalytic detection of nitrite ions present in the solution. TEM images show the PEDOT nanoparticles with an average size of 100-120 nm are uniformly covered on the outer face of rGO-MoS2 nanosheets. The interaction between the PEDOT and rGO-MoS2 is evidenced in the FTIR, XRD and XPS studies, and they produced synergistic effect, resulting enhanced electrocatalytic performance activity towards oxidation of nitrite. Under optimized conditions, the fabricated electrode exhibited remarkably good sensitivity (874.19 µA µM-1 cm-2), low detection limit (LOD) (0.059 µM, S/N = 3), wide linear range (0.001-1 mM) of nitrite with desirable selectivity, long-term stability and reproducibility. Furthermore, the practical feasibility of the fabricated sensor is validated by the successful detection of nitrite ion in some water and milk samples with excellent correlation. Thus, feasible easier synthesis method was adopted first time to fabricate rGO-MoS2-PEDOT nanocomposite nitrite sensor in the milk and water samples with enhanced selectivity, sensitivity and LOD.


Assuntos
Água Potável/análise , Leite/química , Nanocompostos/química , Nitritos/análise , Tanques/análise , Animais , Técnicas Biossensoriais/métodos , Compostos Bicíclicos Heterocíclicos com Pontes/química , Carbono/química , Dissulfetos/química , Técnicas Eletroquímicas/instrumentação , Técnicas Eletroquímicas/métodos , Eletrodos , Contaminação de Alimentos/análise , Grafite/química , Limite de Detecção , Molibdênio/química , Polímeros/química , Reprodutibilidade dos Testes , Poluentes Químicos da Água/análise
7.
J Colloid Interface Sci ; 559: 65-75, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31610306

RESUMO

Electroactive nanofibrous scaffold is a vital tool for the study of the various biological research fields from bioelectronics to regenerative medicine, which can provide cell preferable 3D nanofiber architecture and programmed electrical signal. However, intrinsic non-biodegradability is a major problem that hinders its widespread application in the clinic. Herein, we designed, synthesized, and characterized shell/core poly (3,4-ethylenedioxythiophene) (PEDOT)/chitosan (CS) nanofibers by combining the electrospinning and recrystallization processes. Upon incorporating a trace amount of PEDOT (1.0 wt%), the resultant PEDOT/CS nanofibers exhibited low interfacial charge transfer impedance, high electrochemical stability, high electrical conductivity (up to 0.1945 S/cm), and ultrasensitive piezoelectric property (output voltage of 22.5 mV by a human hair prodding). With such unique electrical and conductive properties, PEDOT/CS nanofibers were further applied to brain neuroglioma cells (BNCs) to stimulate their adhesion, proliferation, growth, and development under an optimal external electrical stimulation (ES) and a pulse voltage of 400 mV/cm. ES-responsive PEDOT/CS nanofibers indeed promoted BNCs growth and development as indicated by a large number and density of axons. The synergetic interplay between external ES and piezoelectric voltage demonstrates new PEDOT-based nanofibers as implantable electroactive scaffolds for numerous applications in nerve tissue engineering, human health monitoring, brain mantle information extraction, and degradable microelectronic devices.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes/química , Quitosana/química , Condutividade Elétrica , Nanofibras/química , Polímeros/química , Testes de Impedância Acústica/métodos , Axônios/metabolismo , Materiais Biocompatíveis/química , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cristalização , Estimulação Elétrica/métodos , Glioma/metabolismo , Humanos
8.
Talanta ; 206: 120252, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31514822

RESUMO

A new electrochemical device based on a combination of nanomaterials such as Printex 6L Carbon and cadmium telluride quantum dots within a poly(3,4-ethylenedioxythiophene) polystyrene sulfonate film was developed for sensitive determination of amoxicillin. The morphological, structural and electrochemical characteristics of the nanostructured material were evaluated using X-ray diffraction, confocal microscopy, transmission electron microscopy and voltammetric techniques. The synergy between these materials increased the electrochemical activity, the electron transfer rate and the electrode surface area, leading to a high magnitude of the anodic peak current for the determination of amoxicillin. The electrochemical determination of the antibiotic was carried out using square-wave voltammetry. Under the optimised experimental conditions, the proposed sensor showed high sensitivity, repeatability and stability to amoxicillin determination, with an analytical curve in the amoxicillin concentration range from 0.90 to 69 µmol L-1, and a low detection limit of 50 nmol L-1. No significant interference in the electrochemical signal of amoxicillin was observed from potential biological interferences and drugs widely used, such as uric acid, paracetamol, urea, ascorbic acid and caffeine. It was demonstrated that without any sample pre-treatment and using a simple measurement device, the sensor could be an alternative method for not only the analysis of pharmaceutical products (commercial tablets) and clinical samples (urine), but also to examine food quality (milk samples).


Assuntos
Amoxicilina/análise , Antibacterianos/análise , Pontos Quânticos/química , Amoxicilina/urina , Animais , Antibacterianos/urina , Compostos Bicíclicos Heterocíclicos com Pontes/química , Compostos de Cádmio/química , Carbono/química , Técnicas Eletroquímicas/instrumentação , Técnicas Eletroquímicas/métodos , Eletrodos , Contaminação de Alimentos/análise , Limite de Detecção , Leite/química , Polímeros/química , Poliestirenos/química , Telúrio/química
9.
ACS Appl Mater Interfaces ; 11(51): 47695-47706, 2019 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-31794187

RESUMO

In this study, we designed a cell-adhesive poly(ethylene glycol) (PEG)-based hydrogel that simultaneously provides topographical and electrical stimuli to C2C12 myoblasts. Specifically, PEG hydrogels with microgroove structures of 3 µm ridges and 3 µm grooves were prepared by micromolding; in situ polymerization of poly(3,4-ethylenedioxythiophene) (PEDOT) was then performed within the micropatterned PEG hydrogels to create a microgrooved conductive hydrogel (CH/P). The CH/P had clear replica patterns of the silicone mold and a conductivity of 2.49 × 10-3 S/cm, with greater than 85% water content. In addition, the CH exhibited Young's modulus (45.84 ± 7.12 kPa) similar to that of a muscle tissue. The surface of the CH/P was further modified via covalent bonding with cell-adhesive peptides to facilitate cell adhesion without affecting conductivity. An in vitro cell assay revealed that the CH/P was cytocompatible and enhanced the cell alignment and elongation of C2C12 myoblasts. The microgrooves and conductivity of the CH/P had the greatest positive effect on the myogenesis of C2C12 myoblasts compared to the other PEG hydrogel samples without conductivity or/and microgrooves, even in the absence of electrical stimulation. Electrical stimulation studies indicated that the combination of topographical and electrical cues maximized the differentiation of C2C12 myoblasts into myotubes, confirming the synergetic effect of incorporating microgroove surface features and a conductive PEDOT component into hydrogels.


Assuntos
Hidrogéis/química , Hidrogéis/farmacologia , Mioblastos/citologia , Mioblastos/efeitos dos fármacos , Polietilenoglicóis/química , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/química , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Módulo de Elasticidade , Estimulação Elétrica , Camundongos , Desenvolvimento Muscular/efeitos dos fármacos , Polímeros/química
10.
Mikrochim Acta ; 187(1): 49, 2019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31848764

RESUMO

A nanocomposite consisting of phytic acid (PA) that was doped with poly(3,4-ethylenedioxy-thiophene) (PEDOT) and modified with copper nanoparticles (CuNPs) was placed on a glassy carbon electrode and then applied in an enzymeless glucose sensor. The undulating PEDOT/PA composite has good conductivity and a large surface area, which was suitable as substrate for the uniform growth of CuNPs. The modified electrode typically operated at a potential near 0.55 V (vs. Ag/AgCl) demonstrated remarkable catalytic activity towards direct oxidation of glucose in NaOH solution (the major limitation of this sensor). Figures of merit include (a) a wide analytical range (5 to 403 µM); (b) high sensitivity (79.27 µA·µM-1·cm-2), (c) a low detection limit (0.28 µM at a signal to noise ratio of 3), and (d) fast response (< 4 s). Graphical abstractA nanocomposite of phytic acid (PA) doped poly(3,4-ethylenedioxy-thiophene) (PEDOT) modified with copper nanoparticles (CuNPs) onto a glassy carbon electrode was prepared by electrochemical strategy. The CuNPs/PEDOT/PA-modified electrodes were applied in enzymeless glucose sensors with high performance.


Assuntos
Técnicas Biossensoriais , Compostos Bicíclicos Heterocíclicos com Pontes/química , Cobre/química , Técnicas Eletroquímicas , Glucose/análise , Nanopartículas Metálicas/química , Ácido Fítico/química , Polímeros/química , Humanos , Tamanho da Partícula , Propriedades de Superfície
11.
Molecules ; 24(23)2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31779257

RESUMO

Due to a significant and prolific activity in the field of design and synthesis of new energetic molecules, it becomes increasingly difficult to introduce new explosophore structures with attractive properties. In this work, we synthesized a trans-bimane-based energetic material-3,7-diamino-2,6-dinitro-1H,5H-pyrazolo-[1,2-a]pyrazole-1,5-dione (4), the structure of which was comprehensively analyzed by a variety of advanced spectroscopic methods and by X-ray crystallo-graphy (with density of 1.845 g·cm-3 at 173 K). Although obtained crystals of 4 contained solvent molecules in their structure, state-of-the-art density functional theory (DFT) computational techniques allowed us to predict that solvent-free crystals of this explosive would preserve a similar tightly packed planar layered molecular arrangement, with the same number of molecules of 4 per unit cell, but with a smaller unit cell volume and therefore higher energy density. Explosive 4 was found to be heat resistant, with an onset decomposition temperature of 328.8 °C, and was calculated to exhibit velocity of detonation in a range of 6.88-7.14 km·s-1 and detonation pressure in the range of 19.14-22.04 GPa, using for comparison both HASEM and the EXPLO 5 software. Our results indicate that the trans-bimane explosophore could be a viable platform for the development of new thermostable energetic materials.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes/química , Substâncias Explosivas/química , Temperatura Alta , Pirazóis/química , Software , Solventes/química , Termodinâmica
12.
Molecules ; 24(22)2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31731797

RESUMO

Recently, the identity of the marine hydrindane natural product (-)-mucosin was revised to the trans-fused structure 6, thereby providing a biogenetic puzzle that remains to be solved. We are now disseminating some of our insights with regard to the possible machinery delivering the established architecture. Aspects with regard to various modes of cyclization in terms of concerted versus stepwise processes are held up against the enzymatic apparatus known to be working on arachidonic acid (8). To provide a contrast to the tentative polyunsaturated fatty acid biogenesis, the structural pattern featured in (-)-mucosin (6) is compared to some marine hydrinane natural products of professed polyketide descent. Our appraisal points to a different origin and strengthens the hypothesis of a polyunsaturated fatty acids (PUFA) as the progenitor of (-)-mucosin (6).


Assuntos
Ácido Araquidônico/química , Produtos Biológicos/química , Compostos Bicíclicos Heterocíclicos com Pontes/química , Indanos/química
13.
Dalton Trans ; 48(44): 16476-16492, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31599913

RESUMO

Bispidones (3,7-diazabicyclo[3.3.1]nonan-9-one) are bicyclic analogues of the natural antiarrhythmic agent, spartein. They can straightforwardly be obtained from two successive Mannich reactions. Reduction of the ketone gives the corresponding bispidol. Substituted bispidones and bispidols offer a large playground by varying the substituents, the configuration of the carbon atoms in position 2 and 4 as well as the conformation of the bicycle. While chair-boat conformers display a strong affinity for κ-opioid receptors, chair-chair bispidines provide adaptable coordination spheres for transition metal and rare-earth ions. Because of their very rich coordination chemistry, substituted bispidines have emerged in various applications of coordination chemistry, such as catalysis, magnetism and medical imaging.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes/química , Compostos Bicíclicos Heterocíclicos com Pontes/metabolismo , Complexos de Coordenação/química , Receptores Opioides kappa/química , Receptores Opioides kappa/metabolismo , Animais , Complexos de Coordenação/metabolismo , Humanos , Metais Terras Raras/química , Conformação Molecular , Radioterapia/métodos , Elementos de Transição/química
14.
Biosens Bioelectron ; 145: 111661, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31539650

RESUMO

The impedance of electrode and photostimulation artifacts (short-duration and high-amplitude spikes) are still hindering the employment of silicon-based neural probe in optogenetics. A fiber-based optrode modified with a double-layer platinum black-poly (3,4ethylenedioxythiophene) PEDOT/poly (4-styrenesulfonate) PSS (Pt-PP) coating has been developed for improvement of neural recording quality and mitigation of photoelectric artifact simultaneously. The Pt-PP coating was made by layer-by-layer electrochemical deposition followed by the ultrasonication and Cyclic Voltammetry (CV) scanning to verify its mechanical and electrochemical stability. Both in-vitro and in-vivo experiments demonstrated that Pt-PP coated optrode had outstanding recording performance (high signal-to-noise ratio about 9.64) and low photoelectric amplitude (850 µV). The artifact recovery time of Pt-PP coated optrode (0.3 ms) after photostimulation was significantly decreased when compared to platinum black (6 ms) or PEDOT/PSS (0.7 ms) coated one which has potential to retain high-quality neural signals in animal experiments. At last, the optogenetics experiments revealed the capability of Pt-PP coated optrode to record the change in neural spike rate with certain spatial resolution and shorter artifact recovery time. These results suggest that Pt-PP coating has great potential for neural electrodes in the application of neuroscience.


Assuntos
Técnicas Biossensoriais , Materiais Revestidos Biocompatíveis/química , Polímeros/química , Animais , Artefatos , Compostos Bicíclicos Heterocíclicos com Pontes/química , Microeletrodos , Neurônios/química , Optogenética/métodos , Platina/química , Silício/química , Ácidos Sulfônicos/química , Ultrassom
15.
Mater Sci Eng C Mater Biol Appl ; 105: 110029, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31546373

RESUMO

The cytocompatibility of cardiomyocytes derived from embryonic stem cells and neural progenitors, which were seeded on the surface of composite films made of graphene oxide (GO) and polypyrrole (PPy-GO) or poly(3,4-ethylenedioxythiophene) (PEDOT-GO) are reported. The GO incorporated in the composite matrix contributes to the patterning of the composite surface, while the electrically conducting PPy and PEDOT serve as ion-to-electron transducers facilitating electrical stimulation/sensing. The films were fabricated by a simple one-step electropolymerization procedure on electrically conducting indium tin oxide (ITO) and graphene paper (GP) substrates. Factors affecting the cell behaviour, i.e. the surface topography, wettability, and electrical surface conductivity, were studied. The PPy-GO and PEDOT-GO prepared on ITO exhibited high surface conductivity, especially in the case of the ITO/PPy-GO composite. We found that for cardiomyocytes, the PPy-GO and PEDOT-GO composites counteracted the negative effect of the GP substrate that inhibited their growth. Both the PPy-GO and PEDOT-GO composites prepared on ITO and GP significantly decreased the cytocompatibility of neural progenitors. The presented results enhance the knowledge about the biological properties of electroactive materials, which are critical for tissue engineering, especially in context stimuli-responsive scaffolds.


Assuntos
Condutividade Elétrica , Eletroquímica , Grafite/farmacologia , Miócitos Cardíacos/citologia , Células-Tronco Neurais/citologia , Polímeros/farmacologia , Animais , Compostos Bicíclicos Heterocíclicos com Pontes/química , Camundongos , Miócitos Cardíacos/efeitos dos fármacos , Células-Tronco Neurais/efeitos dos fármacos , Neurogênese/efeitos dos fármacos , Polímeros/química , Pirróis/química , Água/química
16.
Analyst ; 144(19): 5866-5874, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31482879

RESUMO

To enhance the sensitivity of an aptasensor, a novel strategy was designed to develop an electrochemical aptasensor based on poly(3,4-ethylenedioxy thiophene)-gold nanoflower (PEDOT-AuNF) composites supported on a three-dimensional graphene oxide sponge (GOS). GOS with a three-dimensional sponge-like porous structure, exhibiting excellent electrical conductivity and a large surface area, provided the first amplification of the electrochemical signal for ochratoxin A (OTA) detection. PEDOT-AuNFs, synthesized by an ionic liquid-assisted one-pot method, presented a peculiar hierarchical flower-like structure, a high electroactive surface area, and more binding sites for immobilizing the aptamer molecules by the Au-S bonds. When PEDOT-AuNFs were supported on the surface of GOS by the interaction of the π-π packing between PEDOT and graphene oxide, a synergistic effect was produced to provide the second amplification for the aptasensor. PEDOT-AuNFs/GOS provided an ultrasensitive detection technique by multiple signal amplification for the electrochemical sensing of OTA. Consequently, this strategy not only endowed the aptasensor with high sensitivity but also needed no complicated signal amplification. The electrochemical sensor was fabricated successfully on a glassy carbon electrode to detect OTA with a linear response in the range of 0.01-20 ng L-1 and a limit of detection of 4.9 pg L-1. Moreover, it displayed good specificity, reproducibility and stability. The utilization of the proposed aptasensor for the quantitative determination of OTA in wine indicates that it can find promising applications in detecting OTA and even other mycotoxins in foodstuffs.


Assuntos
Aptâmeros de Nucleotídeos/química , Compostos Bicíclicos Heterocíclicos com Pontes/química , Grafite/química , Nanopartículas Metálicas/química , Ocratoxinas/análise , Polímeros/química , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/instrumentação , Técnicas Eletroquímicas/métodos , Eletrodos , Contaminação de Alimentos/análise , Ouro/química , Limite de Detecção , Reprodutibilidade dos Testes , Vinho/análise
17.
ACS Appl Mater Interfaces ; 11(36): 32778-32786, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31424902

RESUMO

Microelectrode arrays (MEAs) are widely used platforms in bioelectronics to study electrogenic cells. In recent years, the processing of conductive polymers for the fabrication of three-dimensional electrode arrays has gained increasing interest for the development of novel sensor designs. Here, additive manufacturing techniques are promising tools for the production of MEAs with three-dimensional electrodes. In this work, a facile additive manufacturing process for the fabrication of MEAs that feature needle-like electrode tips, so-called µ-needles, is presented. To this end, an aerosol-jet compatible PEDOT:PSS and multiwalled carbon nanotube composite ink with a conductivity of 323 ± 75 S m-1 is developed and used in a combined inkjet and aerosol-jet printing process to produce the µ-needle electrode features. The µ-needles are fabricated with a diameter of 10 ± 2 µm and a height of 33 ± 4 µm. They penetrate an inkjet-printed dielectric layer to a height of 12 ± 3 µm. After successful printing, the electrochemical properties of the devices are assessed via cyclic voltammetry and impedance spectroscopy. The µ-needles show a capacitance of 242 ± 70 nF at a scan rate of 5 mV s-1 and an impedance of 128 ± 22 kΩ at 1 kHz frequency. The stability of the µ-needle MEAs in aqueous electrolyte is demonstrated and the devices are used to record extracellular signals from cardiomyocyte-like HL-1 cells. This proof-of-principle experiment shows the µ-needle MEAs' cell-culture compatibility and functional integrity to investigate electrophysiological signals from living cells.


Assuntos
Condutividade Elétrica , Eletrônica , Tinta , Agulhas , Polímeros/química , Animais , Compostos Bicíclicos Heterocíclicos com Pontes/química , Eletroquímica , Camundongos , Microeletrodos , Nanotubos de Carbono/química , Poliestirenos/química
18.
ACS Appl Mater Interfaces ; 11(37): 34497-34506, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31449380

RESUMO

The rapidly developing field of conducting polymers in organic electronics has many implications for bioelectronics. For biosensing applications, tailoring the functionalities of the conducting polymer's surface is an efficient approach to improve both sensitivity and selectivity. Here, we demonstrated a facile and economic approach for the fabrication of a high-density, negatively charged carboxylic-acid-group-functionalized PEDOT (PEDOT:COOH) using an inexpensive ternary carboxylic acid, citrate, as a dopant. The polymerization efficiency was significantly improved by the addition of LiClO4 as a supporting electrolyte yielding a dense PEDOT:COOH sensing interface. The resulting PEDOT:COOH interface had a high surface density of carboxylic acid groups of 0.129 µmol/cm2 as quantified by the toluidine blue O (TBO) staining technique. The dopamine response measured with the PEDOT:COOH sensing interface was characterized by cyclic voltammetry with a significantly reduced ΔEp of 90 mV and a 3-fold increase in the Ipa value compared with those of the nonfunctionalized PEDOT sensing interface. Moreover, the cyclic voltammetry and electrochemical impedance spectroscopy results demonstrated the increased electrode kinetics and highly selective discrimination of dopamine (DA) in the presence of the interferents ascorbic acid (AA) and uric acid (UA), which resulted from the introduction of negatively charged carboxylic acid groups. The negatively charged carboxylic acid groups could favor the transfer, preconcentration, and permeation of positively charged DA to deliver improved sensing performance while repelling the negatively charged AA and UA interferents. The PEDOT:COOH interface facilitated measurement of dopamine over the range of 1-85 µM, with a sensitivity of 0.228 µA µM-1, which is 4.1 times higher than that of a nonfunctionalized PEDOT electrode (0.055 µA µM-1). Our results demonstrate the feasibility of a simple and economic fabrication of a high-density PEDOT:COOH interface for chemical sensing, which also has the potential for coupling with other biorecognition molecules via carboxylic acid moieties for the development of a range of advanced PEDOT-based biosensors.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes/química , Ácido Cítrico/química , Dopamina/análise , Técnicas Eletroquímicas , Polímeros/química , Ácido Ascórbico/química , Limite de Detecção , Ácido Úrico/química
19.
Mater Sci Eng C Mater Biol Appl ; 103: 109733, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31349519

RESUMO

Helicobacter pylori (H. pylori) immunosensor based on platinum nanoparticles/poly(3,4-ethylenedioxythiophene)/reduced graphene oxide (Ptnano/PEDOT/red-GOx) modified gold electrode (Au-ET) was stepwise fabricated for the detection of cytotoxin-associated gene A antibody (CagA antibody). H. pylori is a microaerophillic and a Gram-negative bacteria that causes gastric ulcer leading eventually to adenocarcinoma (gastric cancer) in the later stage. H. pylori colonizes inner lining of human stomach. The developed diagnostic sensing interface would allow H. pylori (stomach infection) detection in early stage and would be a great contribution in clinical laboratories. In order to fabricate the immunosensor, CagA antigen was immobilized over the Ptnano/PEDOT/red-GOx modified Au-ET. Afterwards, the modified electrode was used for immuno-sensing of H. pylori specific Cag A antibodies in serum. At lower voltage the modified Ptnano/PEDOT/red-GOx/Au-ET shows an amplified sensing at the interface that makes the sensor more sensitive and specific. CagA is a virulence factor produced by H. pylori was determined by sudden decrease in the current. The laboratory synthesized nano composites were characterised by Scanning Electron Microscopy (SEM) and Atomic force microscopy (AFM) studies. The sensor had excellent linear range of 0.1 ng/ml to 30 ng/ml by limiting the detection range up to 0.1 ng/ml. Moreover, the novel immunosensor formed had good accuracy, precision and reliability. The immunosensor also showed an excellent storage stability by retaining 60-70% of its initial activity until 60 days kept at 4 °C. Highly sensitive interface of CagA antigen@Ptnano/PEDOT/red-GOx/Au-ET shows a promising future for H. pylori detection in diagnosis of stomach ulcer and stomach cancer.


Assuntos
Anticorpos Antibacterianos , Antígenos de Bactérias , Proteínas de Bactérias , Compostos Bicíclicos Heterocíclicos com Pontes/química , Materiais Revestidos Biocompatíveis/química , Técnicas Eletroquímicas , Infecções por Helicobacter , Helicobacter pylori , Nanocompostos/química , Platina/química , Polímeros/química , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Antígenos de Bactérias/química , Antígenos de Bactérias/imunologia , Proteínas de Bactérias/química , Proteínas de Bactérias/imunologia , Eletrodos , Infecções por Helicobacter/sangue , Infecções por Helicobacter/imunologia , Helicobacter pylori/imunologia , Helicobacter pylori/metabolismo , Humanos , Imunoensaio
20.
Eur J Med Chem ; 179: 791-804, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31288128

RESUMO

Advances in the field of boron chemistry have expanded the application of this element in Medicinal Chemistry. Boron-containing compounds represent a new class for medicinal chemists to use in their drug designs. Bortezomib (Velcade®), a dipeptide boronic acid approved by the FDA in 2003 for treatment of multiple myeloma, paved the way for the discovery of new boron-containing compounds. After its approval, two other boron-containing compounds have been approved, tavaborole (Kerydin®) for the treatment of onychomicosis and crisaborole (Eucrisa®) for the treatment of mild to moderate atopic dermatitis. A number of boron-containing compounds have been described and evaluated for a plethora of therapeutic applications. The present review is intended to highlight the recent advances related to boron-containing compounds and their therapeutic applications. Here, we focused only in those most biologically active compounds with proven in vitro and/or in vivo efficacy in the therapeutic area published in the last years.


Assuntos
Compostos de Boro/uso terapêutico , Bortezomib/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Dermatite Atópica/tratamento farmacológico , Mieloma Múltiplo/tratamento farmacológico , Onicomicose/tratamento farmacológico , Animais , Compostos de Boro/síntese química , Compostos de Boro/química , Bortezomib/síntese química , Bortezomib/química , Compostos Bicíclicos Heterocíclicos com Pontes/síntese química , Compostos Bicíclicos Heterocíclicos com Pontes/química , Desenho de Fármacos , Humanos
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