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1.
Int J Nanomedicine ; 15: 4825-4845, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32753868

RESUMO

Background: Nanosized drug delivery systems (NDDSs) have shown excellent prospects in tumor therapy. However, insufficient penetration of NDDSs has significantly impeded their development due to physiological instability and low passive penetration efficiency. Methods: Herein, we prepared a core cross-linked pullulan-modified nanosized system, fabricated by visible-light-induced diselenide bond cross-linked method for transporting ß-Lapachone and doxorubicin prodrug (boronate-DOX, BDOX), to improve the physiological stability of the NDDSs for efficient passive accumulation in tumor blood vessels (ß-Lapachone/BDOX-CCS). Additionally, ultrasound (US) was utilized to transfer ß-Lapachone/BDOX-CCS around the tumor vessel in a relay style to penetrate the tumor interstitium. Subsequently, ß-Lapachone enhanced ROS levels by overexpressing NQO1, resulting in the transformation of BDOX into DOX. DOX, together with abundant levels of ROS, achieved synergistic tumor therapy. Results: In vivo experiments demonstrated that ultrasound (US) + cross-linked nanosized drug delivery systems (ß-Lapachone/BDOX-CCS) group showed ten times higher DOX accumulation in the tumor interstitium than the non-cross-linked (ß-Lapachone/BDOX-NCS) group. Conclusion: Thus, this strategy could be a promising method to achieve deep penetration of NDDSs into the tumor.


Assuntos
Doxorrubicina/uso terapêutico , Nanopartículas/química , Naftoquinonas/uso terapêutico , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Pró-Fármacos/uso terapêutico , Ultrassonografia , Animais , Ácidos Borônicos/química , Permeabilidade Capilar/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Reagentes para Ligações Cruzadas/química , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos , Endocitose/efeitos dos fármacos , Feminino , Glucanos/química , Células Hep G2 , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Naftoquinonas/farmacocinética , Tamanho da Partícula , Pró-Fármacos/farmacocinética , Espécies Reativas de Oxigênio/metabolismo , Distribuição Tecidual/efeitos dos fármacos
2.
J Chromatogr A ; 1627: 461423, 2020 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-32823118

RESUMO

A novel stationary phase co-modified with N-isopropyl acrylamide (NIPAM) and 3-aminophenylboronic acid copolymer on the silica was synthesized through atom transfer radical polymerization (ATRP) reaction for performing mixed-mode and boronate affinity chromatography. The prepared functionalized silica was characterized using Fourier transform infrared spectrometry (FT-IR), elemental analysis (EA) and thermogravimetric analysis (TGA), scanning electron micrographs (SEM) and Brunauer-Emmett-Teller (BET) measurements. The prepared column named Sil-PBA-NIPAM showed great separation performance for hydrophobic, hydrophilic, positional isomer, acidic and alkaline compounds. Besides, the mixture of cis-diol and non-cis-diol compounds was used to prove that the developed column also has potential to capture and enrich cis-diol compounds. The prepared column possesses merits of time-saving, high selectivity to cis-diol compounds and molecular-planarity selectivity compared with two commercial single-mode columns. The theoretical plates of material can reach to 57472 and the column has good hydrolysis stability and batch-to-batch reproducibility. In summary, the prepared column possesses good hydrophilicity, hydrophobicity, molecular-planarity selectivity and boronate affinity abilities for the analysis of various compounds.


Assuntos
Acrilamidas/química , Ácidos Borônicos/química , Cromatografia/métodos , Polímeros/química , Ácido Benzoico/análise , Cromatografia de Fase Reversa , Hidrólise , Interações Hidrofóbicas e Hidrofílicas , Fenóis/análise , Polimerização , Reprodutibilidade dos Testes , Dióxido de Silício/química , Espectroscopia de Infravermelho com Transformada de Fourier , Termogravimetria
3.
Food Chem ; 332: 127394, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32610259

RESUMO

In this study, we present the preparation of a new reverse-phase/phenylboronic-acid (RP/PBA)-type mixed-mode magnetic solid-phase extraction (MSPE) adsorbent for use in the cleanup of amatoxin- and phallotoxin-containing samples intended for ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis. Further, the RP/PBA magnetic microspheres have phenyl and phenylboronic acid groups on their surfaces that selectively adsorb amatoxins and phallotoxins through hydrophobic, π-π, and boronate affinity, significantly reducing matrix effects in UPLC-MS/MS analysis. After systematic optimization, all the standard calibration curves expressed satisfactory linearity (r > 0.9930), limits of detection (0.3 µg/kg), and recovery (97.6%-114.2%). Compared with other reported methods, this method also has the advantages of simple, fast, and efficient operation using relatively small amounts of the MSPE adsorbent. Furthermore, the method was successfully applied in a poisoning incident caused by Lepiota brunneoincarnata Chodat & C. Martín ingestion.


Assuntos
Amanitinas/análise , Ácidos Borônicos/química , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia de Fase Reversa/métodos , Imãs/química , Espectrometria de Massas em Tandem/métodos , Adsorção , Amanitinas/isolamento & purificação , Limite de Detecção , Microesferas , Extração em Fase Sólida
4.
Nat Protoc ; 15(5): 1742-1759, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32269382

RESUMO

[18F]6-fluoro-L-DOPA ([18F]FDOPA) is a diagnostic radiopharmaceutical for positron emission tomography (PET) imaging that is used to image Parkinson's disease, brain tumors, and focal hyperinsulinism of infancy. Despite these important applications, [18F]FDOPA PET remains underutilized because of synthetic challenges associated with accessing the radiotracer for clinical use; these stem from the need to radiofluorinate a highly electron-rich catechol ring in the presence of an amino acid. To address this longstanding challenge in the PET radiochemistry community, we have developed a one-pot, two-step synthesis of high-molar-activity [18F]FDOPA by Cu-mediated fluorination of a pinacol boronate (BPin) precursor. The method is fully automated, has been validated to work well at two separate sites (an academic facility with a cyclotron on site and an industry lab purchasing [18F]fluoride from an outside vendor), and provides [18F]FDOPA in reasonable radiochemical yield (2.44 ± 0.70 GBq, 66 ± 19 mCi, 5 ± 1%), excellent radiochemical purity (>98%) and high molar activity (76 ± 30 TBq/mmol, 2,050 ± 804 Ci/mmol), n = 26. Herein we report a detailed protocol for the synthesis of [18F]FDOPA that has been successfully implemented at two sites and validated for production of the radiotracer for human use.


Assuntos
Ácidos Borônicos/química , Técnicas de Química Sintética/métodos , Cobre/química , Di-Hidroxifenilalanina/análogos & derivados , Glicóis/química , Di-Hidroxifenilalanina/síntese química , Radioisótopos de Flúor , Halogenação
5.
Food Chem ; 324: 126892, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32339789

RESUMO

To investigate calpain's effect on protein degradation, myowater properties, and the water-holding capacity (WHC), porcine longissimus muscles were incubated with control buffer, PD150,606 (calpain-specific inhibitor) and MG-262 (multiple-protease inhibitor) and assigned to an ageing period of 1, 4 or 7 d. Over 7 d of storage, no significant differences (P > 0.05) were observed in desmin or integrin expression between the MG-262 and PD150,606 groups, which indicated that calpain played a major role in protein proteolysis. Compared to those in the control group, muscle samples subjected to PD150,606 and MG-262 exhibited higher water mobility and a poorer WHC. Additionally, there were no significant differences in myowater properties or the WHC between the two groups at 1 d postmortem (P > 0.05). Calpain regulated the distribution and mobility of myowater, which contributed to a higher WHC in the early postmortem period (before 4 d), but other proteases tended to take over at a later stage.


Assuntos
Calpaína/metabolismo , Músculo Esquelético/química , Água/metabolismo , Acrilatos/química , Acrilatos/metabolismo , Animais , Ácidos Borônicos/química , Ácidos Borônicos/metabolismo , Calpaína/antagonistas & inibidores , Desmina/metabolismo , Armazenamento de Alimentos , Integrinas/metabolismo , Carne/análise , Músculo Esquelético/metabolismo , Inibidores de Proteases/química , Inibidores de Proteases/metabolismo , Proteólise , Suínos , Água/análise
6.
Anal Bioanal Chem ; 412(7): 1509-1520, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32002580

RESUMO

Highly specific enrichment of N-linked glycopeptides from complex biological samples is crucial prior to mass spectrometric analysis. In this work, a hydrophilic metal-organic framework composite is prepared by the growth of UiO-66-NH2 on graphene sheets, followed by its post-synthetic modification to attach boronic acid to form GO@UiO-66-PBA. The fabrication of graphene oxide-MOF composite results in enhanced surface area with improved thermal and chemical stability. The synthesized MOF nanocomposite is characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and BET. A crystalline structure with high porosity offering large surface area and good hydrophilicity of the nanocomposite assists as an enrichment tool in glycoproteomics. The GO@UiO-66-PBA nanocomposite selectively enriches N-linked glycopeptides from tryptic digests of horseradish peroxidase (HRP) and immunoglobulin (IgG). GO@UiO-66-PBA nanoparticles show a low detection limit (1 fmol) and good specificity (1:200), reusability and reproducibility for N-linked glycopeptide enrichment from IgG digest. The binding capacity of GO@UiO-66-PBA is 84 mg/g for protein concentration, with a good recovery of 86.5%. A total of 372 N-linked glycopeptides corresponding to different glycoproteins are identified from only 1 µL of human serum digest. Thus, the presented research work can be an efficient separation platform for N-linked glycopeptide enrichment from complex samples, which can be extended to cost-effective routine analysis. Graphical abstract.


Assuntos
Ácidos Borônicos/química , Glicopeptídeos/química , Estruturas Metalorgânicas/química , Grafite/química , Peroxidase do Rábano Silvestre/química , Humanos , Microscopia Eletrônica de Varredura , Reprodutibilidade dos Testes
7.
Macromol Rapid Commun ; 41(6): e1900586, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32022359

RESUMO

Orthogonal dynamic covalent self-assembly is used as a facile method for constructing polymer hollow nanocapsules (NCs) and thin films. The bifunctional precursor 4-formylphenylboronic acid is symmetrically installed with a boronic acid group for the boroxine linkage, and an aldehyde group for the Schiff base reaction which can react with twofold symmetry linkers ethylenediamine and para phenylenediamine to attain polymer NCs and nanosheets. Owing to the reversibility of the imine linkages, the mutual morphological transformation between polymer NCs and thin films via an amine-imine-exchange strategy is successfully achieved. Multiple reversible covalent bonds allow the control the release of the load in polymer NCs using different techniques. This may be useful for designing stimulus-responsive smart materials.


Assuntos
Benzaldeídos/química , Ácidos Borônicos/química , Etilenodiaminas/química , Iminas/química , Nanocápsulas/química , Fenilenodiaminas/química , Polímeros/química , Polímeros/síntese química , Aldeídos/química , Aminas/química , Nanocápsulas/ultraestrutura , Nanoestruturas/química , Nanoestruturas/ultraestrutura , Bases de Schiff/química , Propriedades de Superfície
8.
J Med Chem ; 63(6): 3004-3027, 2020 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-32057241

RESUMO

ß-Tryptase, a homotetrameric serine protease, has four identical active sites facing a central pore, presenting an optimized setting for the rational design of bivalent inhibitors that bridge two adjacent sites. Using diol, hydroxymethyl phenols or benzoyl methyl hydroxamates, and boronic acid chemistries to reversibly join two [3-(1-acylpiperidin-4-yl)phenyl]methanamine core ligands, we have successfully produced a series of self-assembling heterodimeric inhibitors. These heterodimeric tryptase inhibitors demonstrate superior activity compared to monomeric modes of inhibition. X-ray crystallography validated the dimeric mechanism of inhibition, and compounds demonstrated high selectivity against related proteases, good target engagement, and tryptase inhibition in HMC1 xenograft models. Screening 3872 possible combinations from 44 boronic acid and 88 diol derivatives revealed several combinations that produced nanomolar inhibition, and seven unique pairs produced greater than 100-fold improvement in potency over monomeric inhibition. These heterodimeric tryptase inhibitors demonstrate the power of target-driven combinatorial chemistry to deliver bivalent drugs in a small molecule form.


Assuntos
Inibidores de Proteases/química , Inibidores de Proteases/farmacologia , Triptases/antagonistas & inibidores , Animais , Ácidos Borônicos/química , Ácidos Borônicos/farmacologia , Cristalografia por Raios X , Feminino , Humanos , Camundongos , Simulação de Acoplamento Molecular , Conformação Proteica/efeitos dos fármacos , Multimerização Proteica/efeitos dos fármacos , Triptases/química , Triptases/metabolismo
9.
Molecules ; 25(2)2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31936861

RESUMO

In our current work, we have reported the first cobalt-catalyzed cross-coupling of arylboronic acid with alkyl/aryl phosphites under mild conditions. The reaction was carried out in the presence of zinc powder as an additive and ter-pyridine as a ligand. The use of non-precious cobalt salt makes the protocol advantageous, as it is inexpensive and more abundant than the previously used methods where precious metal salts (Pd and Pt) were used. The reaction has a wide substrate scope and the products were obtained in good yields.


Assuntos
Ácidos Borônicos/química , Cobalto/química , Zinco/química , Catálise
10.
Chemistry ; 26(9): 1922-1927, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-31738451

RESUMO

The synthesis of a diverse range of heterobiaryls has been achieved by a transition-metal-free sp2 -sp2 cross-coupling strategy using lithiated heterocycle, aryl or heteroaryl boronic ester and an electrophilic halogen source. The construction of heterobiaryls was carried out through electrophilic activation of the aryl-heteroaryl boronate complex, which triggered 1,2-migration from boron to the carbon atom. Subsequent oxidation of the intermediate boronic ester afforded heterobiaryls in good yield. A comprehensive 11 B NMR study has been conducted to support the mechanism. The cross coupling between two nucleophilic cross coupling partners without transition metals reveals a reliable manifold to procure heterobiaryls in good yields. Various heterocycles like furan, thiophene, benzofuran, benzothiophene, and indole are well tolerated. Finally, we have successfully demonstrated the gram scale synthesis of the intermediates for an anticancer drug and OLED material using our methodology.


Assuntos
Ácidos Borônicos/química , Compostos Heterocíclicos/química , Catálise , Compostos Heterocíclicos/síntese química , Paládio/química , Teoria Quântica , Elementos de Transição/química
11.
Chem Biodivers ; 17(1): e1900436, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31705573

RESUMO

A facile method was developed for synthesis of boronic acid-functionalized silica nanocomposites (SiO2 -BA) by 'thiol-ene' click reaction, where silica nanoparticles were synthesized by using tetraethoxysilane (TEOS) and γ-mercaptopropyl trimethoxysilane (γ-MPTS) as precursors. The morphology and structure properties of the resultant SiO2 -BA were characterized by transmission electronic microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), and Brunner-Emmet-Teller measurements (BET). The adsorption behavior of the SiO2 -BA for glycoproteins was evaluated. Under the optimized conditions, the SiO2 -BA exhibited higher adsorption capacity towards glycoproteins (ovalbumin, OVA, 7.64 µmol/g) than non-glycoproteins (bovine serum albumin, BSA, 0.83 µmol/g). In addition, the practicality of the SiO2 -BA was further assessed by selective enrichment of glycoproteins from egg white samples.


Assuntos
Ácidos Borônicos/química , Glicoproteínas/química , Nanocompostos/química , Dióxido de Silício/química , Adsorção , Clara de Ovo/química , Estrutura Molecular , Tamanho da Partícula , Dióxido de Silício/síntese química , Propriedades de Superfície
12.
Chemosphere ; 242: 125135, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31669991

RESUMO

The anionic form-dependent binding interaction of halo-phenolic substances with human transthyretin (hTTR) has been observed previously. This indicates that ionizable compounds should be the primary focus in screening potential hTTR disruptors. Here, the potential binding potency of halo-benzoic acids, halo-benzenesulfonic acids/sulfates and halo-phenylboronic acids with hTTR was determined and analyzed by competitive fluorescence displacement assay integrated with computational methods. The laboratorial results indicated that the three test groups of model compounds exhibited a distinct binding affinity to hTTR. All the tested halo-phenylboronic acids, some of the tested halo-benzoic acids and halo-benzenesulfonic acids/sulfates were shown to be inactive with hTTR. Other halo-benzoic acids and halo-benzenesulfonic acids/sulfates were moderate and/or weak hTTR binders. The binding affinity of halo-benzoic acids and halo-benzenesulfonic acids/sulfates with hTTR was similar. The low distribution ability of the model compounds from water to hTTR may be the reason why they exhibited the binding potency observed with hTTR. By introducing other highly hydrophobic compounds, we observed that the binding affinity between compounds and hTTR increased with increasing molecular hydrophobicity. Those results indicated that the highly hydrophobic halo-benzoic acids and halo-benzenesulfonic acids/sulfates may be high-priority hTTR disruptors. Finally, a binary classification model was constructed employing three predictive variables. The sensitivity (Sn), specificity (Sp), predictive accuracy (Q) values of the training set and validation set were >0.83, indicating that the model had good classification performance. Thus, the binary classification model developed here could be used to distinguish whether a given ionizable compound is a potential hTTR binder or not.


Assuntos
Benzenossulfonatos/química , Benzoatos/química , Ácidos Borônicos/química , Modelos Químicos , Pré-Albumina/química , Humanos , Fenóis , Pré-Albumina/metabolismo
13.
J Chromatogr A ; 1609: 460510, 2020 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-31515077

RESUMO

In this study, a novel phenyl-boronic acid polymeric monolith (PBAPM) in polyether ether ketone (PEEK) tube was fabricated. The inner wall of PEEK tube was modified with mussel inspired polydopamine layer to firmly bond PBAPM, so as to avoid the outflow of PBAPM from PEEK tube and improve the service life and application scope of PBAPM. The PBAPM was synthesized by initiator-free ring-opening polymerization based on our previous work. The boric acid groups provided B-N coordination sites, as well as the hydrophobic amino and epoxy monomers provided hydrophobic interaction sites. Due to the synergistic effect of hydrophobic interaction and B-N coordination, the PBAPM exhibited excellent binding amounts for nitrogen-containing sulfonamides (SAs). In addition, the PBAPM possessed excellent stability, rigidity and permeability. Therefore, the PBAPM was used as solid phase microextraction (SPME) material for enrichment and separation of SAs from aqueous samples. The PBAPM SPME was optimized in detail, and combined with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis for simultaneous determination of 10 kinds of SAs from tap, lake and river water. Using only 1 mL of water samples, limit of quantitation of SAs could reach 0.54-4.5 ng L-1. Recoveries of standard spiked SAs from water samples were between 82.0% and 105.4%, with intra-day and inter-day relative standard deviation ranging from 3.3% to 5.6% and 4.2% to 8.1%, respectively. The PBAPM SPME combined with UPLC-MS/MS method shown better or similar recoveries, and used fewer samples than previous methods. These results demonstrated that the PBAPM could selectively separate and enrich ultra-trace nitrogen-containing SAs from aqueous samples.


Assuntos
Ácidos Borônicos/química , Cromatografia Líquida de Alta Pressão/métodos , Polimerização , Polímeros/química , Microextração em Fase Sólida , Sulfonamidas/análise , Espectrometria de Massas em Tandem/métodos , Sulfonamidas/química , Água/química , Poluentes Químicos da Água/análise
14.
Anal Chim Acta ; 1093: 61-74, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31735216

RESUMO

Covalent organic frameworks (COFs) have been increasingly employed in separation science, including sample preparation. Herein we fabricated the amino bearing core-shell structured COFs nanospheres [Fe3O4@TpBD(NH2)2], and a novel magnetic boronate affinity adsorbent was synthesized by postsynthetic modification of the Fe3O4@TpBD(NH2)2 with 2-formylphenylboronic acid. The magnetic boronate affinity adsorbent possesses fast magnetic response and high binding capacity up to 1037 µmol g-1 for dopamine. Besides, it was used as an adsorbent for extraction of urinary monoamine neurotransmitters at neutral pH. A method for detection of the monoamine neurotransmitters was developed by coupling the magnetic solid phase extraction with high-performance liquid chromatography-fluorescence detection. Under the optimized conditions, a good analytical method was obtained in the linear dynamic range of 2-200 ng mL-1 with R2 between 0.9917 and 0.9966, with low limit of detection (0.31-0.54 ng mL-1) and limit of quantification (1.04-1.80 ng mL-1). The recoveries of the monoamine neurotransmitters were in the range of 86.3-115%, with relative standard deviations of 2.34-10.5% (intra-day) and 2.84-14.4% (inter-day). The method was successfully applied to the determination of the monoamine neurotransmitters in human urine samples. This work is of great importance for preparing functionalized core-shell structured magnetic covalent organic framework nanospheres, it also demonstrates the feasibility of the functionalized magnetic COFs as adsorbents in sample pretreatment.


Assuntos
Monoaminas Biogênicas/urina , Ácidos Borônicos/química , Catecolaminas/urina , Estruturas Metalorgânicas/química , Nanosferas/química , Neurotransmissores/urina , Adsorção , Cromatografia Líquida de Alta Pressão/métodos , Humanos , Limite de Detecção , Nanopartículas de Magnetita/química , Estruturas Metalorgânicas/síntese química , Porosidade , Reprodutibilidade dos Testes , Extração em Fase Sólida/métodos
15.
Eur J Med Chem ; 185: 111783, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31732257

RESUMO

Over the past decade, many drug discovery endeavors have been invested in targeting the serine proteases prolyl oligopeptidase (POP) for the treatment of Alzheimer's and Parkinson's disease and, more recently, epithelial cancers. Our research group has focused on the discovery of reversible covalent inhibitors, namely nitriles, to target the catalytic serine residue in this enzyme. While there have been many inhibitors discovered containing a nitrile to covalently bind to the catalytic serine, we have been investigating others, particularly boronic acids and boronic esters, the latter of which have been largely unexplored as covalent warheads. Herein we report a series of computationally-designed POP boronic ester pro-drug inhibitors exhibiting nanomolar-potencies in vitro as their active boronic acid species. These easily-accessible (1-2 step syntheses) compounds could facilitate future biochemical and biological studies of this enzyme's role in neurodegenerative diseases and cancer progression.


Assuntos
Ácidos Borônicos/farmacologia , Descoberta de Drogas , Ésteres/farmacologia , Pró-Fármacos/farmacologia , Serina Endopeptidases/metabolismo , Ácidos Borônicos/síntese química , Ácidos Borônicos/química , Relação Dose-Resposta a Droga , Ésteres/síntese química , Ésteres/química , Humanos , Conformação Molecular , Simulação de Acoplamento Molecular , Pró-Fármacos/síntese química , Pró-Fármacos/química , Relação Estrutura-Atividade
16.
Talanta ; 208: 120447, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31816774

RESUMO

The selective fluorescence sensing of hypochlorite (ClO-) was achieved at pH 7.4 by a simple analytical procedure through the fluorescence quenching of autoclave synthesized carbon dots (CDs), which used as precursor an adduct formed between 3-aminophenylboronic acid (APBA) and alizarin red S (ARS). The use of this adduct allowed the preparation of CDs with a red shifted emission (560 nm) and excitation in the visible range (490 nm). Quantification of hypochlorite was achieved at physiological pH (pH 7.4) in aqueous solutions by fluorescence quenching with a linearity range of 0-200 µM (limit of detection of 4.47 µM, and limit of quantification of 13.41 µM). The selectivity of hypochlorite sensing was confirmed by comparison with other potential analytes, such as glucose, fructose and hydrogen peroxide. Finally, the validity of the proposed assay was further demonstrated by performing recovery assays in different matrices. Thus, this CDs allows the fluorescent sensing of ClO- with spectral properties more suitable for in vitro/in vivo applications.


Assuntos
Antraquinonas/química , Ácidos Borônicos/química , Carbono/química , Ácido Hipocloroso/análise , Fluorescência , Ouro/química , Ácido Hipocloroso/química , Nanopartículas Metálicas/química
17.
Anal Chim Acta ; 1094: 70-79, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31761049

RESUMO

To explore how hypochlorous acid (HClO) affects human health, a highly sensitive, selective, and trace detection method for hypochlorite (ClO-) is crucial for determining its non-negligible function in both environment and living systems. Herein, a dicyanoisophorone-phenylboronic acid-based novel ratiometric near-infrared fluorescent probe (Probe 1) was designed for the rapid and specific detection of ClO- based on the intramolecular charge transfer (ICT) mechanism. Excess addition of HClO to the Probe 1 solution, 186-times ratio (I652/I582) augment were gained. And this probe provided a colorimetric and ratiometric fluorescence response to ClO- with a high selectivity, a rapid response (within 30 s), and had an extremely low detection limit (15.7 nM). In addition, owing to the good sensing properties and low cytotoxicity of Probe 1, it can be used to expediently visualize exogenous ClO- in HepG2 cells and endogenous ClO- in RAW264.7 macrophage cells. Furthermore, the probe was successfully used for the bioimaging of zebrafish with an acute inflammation. Thus, Probe 1 is a promising vehicle to identify the level of HClO in animals with associated diseases.


Assuntos
Ácidos Borônicos/química , Corantes Fluorescentes/química , Ácido Hipocloroso/análise , Inflamação/metabolismo , Nitrilos/química , Animais , Ácidos Borônicos/síntese química , Ácidos Borônicos/toxicidade , Colorimetria/métodos , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/toxicidade , Células Hep G2 , Humanos , Ácido Hipocloroso/metabolismo , Inflamação/induzido quimicamente , Limite de Detecção , Lipopolissacarídeos , Camundongos , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos , Nitrilos/síntese química , Nitrilos/toxicidade , Células RAW 264.7 , Peixe-Zebra
18.
Anal Chim Acta ; 1095: 204-211, 2020 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-31864624

RESUMO

The abnormal expression of sialic acids (SAs) on cells and tissues is closely related to various pathophysiological states. Here we applied phenylboronic acid (PBA) functionalized graphitic carbon nitride fluorescent quantum dots (PCQDs) with sizes from 3 to 5 nm in efficient and selective labeling SAs on the surface of living cells and tissues. With abundant PBA in their structure, the water soluble PCQDs showed the relative SA level on the cell surface via selectively and efficiently staining different cell lines in 30 min and revealed that M1 macrophages may express more SAs on their surfaces compared with M0 and M2. The distinct demarcation of cancerous and para-noncancerous areas on cancer tissue sections was showed by PCQDs staining. PCQDs with their high selectivity, stable photoluminescence, low cost, and nontoxicity can be an ideal SA fluorescent probe for living cells and tissues.


Assuntos
Corantes Fluorescentes/química , Grafite/química , Ácido N-Acetilneuramínico/análise , Compostos de Nitrogênio/química , Pontos Quânticos/química , Animais , Ácidos Borônicos/química , Ácidos Borônicos/toxicidade , Linhagem Celular Tumoral , Corantes , Corantes Fluorescentes/toxicidade , Grafite/toxicidade , Humanos , Pulmão/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos , Ácido N-Acetilneuramínico/metabolismo , Compostos de Nitrogênio/toxicidade , Pontos Quânticos/toxicidade , Células RAW 264.7 , Coloração e Rotulagem
19.
Mikrochim Acta ; 186(12): 774, 2019 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-31728646

RESUMO

An antibody-free immunoassay that makes use of a boronate affinity molecularly imprinted polymer (MIP) and surface enhanced Raman scattering (SERS) tags is described. It was applied to the specific determination of the carcinoembryonic antigen (CEA) in human serum. For the preparation of the boronate affinity array, a polymer capable of adsorbing glycoproteins was first synthesized on the surface of a glass slide with four spots using 4-vinylbenzeneboronic acid (VPBA) as the functional monomer, ethylene glycol dimethacrylate (EGDMA) as the crosslinking agent, and ethylene glycol and cyclohexanol as porogens. The surface of the VPBA-Co-EGDMA can bind target glycoproteins. After specific capture of the glycoprotein, a "MIP-target glycoprotein-SERS tag" sandwich structure was formed by covalent interaction between the SERS nanotag (consisting of gold nanoparticles and 4-mercaptophenylboronic acid [MPBA]). CEA can be quantified in spiked serum with a detection limit of 0.1 ng·mL-1 via the specific Raman band at 1098 cm-1. Graphical abstractSchematic representation of the boronate affinity molecularly imprinted polymer (MIPs) array-based SERS sensor for rapid and sensitive detection of the carcinoembryonic antigen (CEA) from human serum. The boronate affinity MIPs array are used as capture probes, and MPBA@AuNPs are used as SERS tags.


Assuntos
Ácidos Borônicos/química , Antígeno Carcinoembrionário/sangue , Imunoensaio , Impressão Molecular , Polímeros/química , Anticorpos/sangue , Anticorpos/imunologia , Antígeno Carcinoembrionário/imunologia , Ouro/química , Humanos , Nanopartículas Metálicas/química , Tamanho da Partícula , Análise Espectral Raman , Propriedades de Superfície
20.
ACS Appl Mater Interfaces ; 11(50): 46585-46590, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31763806

RESUMO

Messenger RNA (mRNA) represents an emerging class of nucleic acid therapeutics for genome editing and genetic disease treatment. Delivering exogenous mRNA selectively to cells, however, remains a main challenge to broaden the biomedical application of mRNA and develop targeted gene therapy. Herein, we report cell-selective mRNA delivery and CRISPR/Cas9 genome editing by modulating the interface of phenylboronic acid (PBA) derived lipid nanoparticles (NPs) and cellular surface sialic acid (SA). We design a cationic lipid featuring a PBA group, PBA-BADP, to self-assemble with mRNA into nanoparticles via electrostatic interactions. Importantly, these nanoparticles present free PBA groups on their surface, showing an enhanced cellular uptake by SA-overexpressing cancer cells via the interfacial PBA/SA interaction. It is shown that PBA-BADP/mRNA NPs transfection results in 300 times higher luciferase reporter gene expression in cancer cells than that in noncancer cells. Moreover, we demonstrate that the delivery of tumor suppressor p53 mRNA using PBA-BADP selectively prohibits cancer cell growth, while PBA-BADP/Cas9 mRNA NPs delivery knocks out gene expression of HeLa cancer cells in a much higher efficiency than noncancer cells. We believe these findings could further extend the modulation of PBA and cellular SA interface to advance mRNA delivery and genome editing for new gene therapy.


Assuntos
Técnicas de Transferência de Genes , Lipídeos/farmacologia , Nanopartículas/química , RNA Mensageiro/farmacologia , Ácidos Borônicos/química , Sistemas CRISPR-Cas/efeitos dos fármacos , Sistemas CRISPR-Cas/genética , Edição de Genes/métodos , Terapia Genética , Células HeLa , Humanos , Lipídeos/química , Ácido N-Acetilneuramínico/química , Ácido N-Acetilneuramínico/metabolismo , RNA Mensageiro/química , Transfecção/métodos
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