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1.
Chem Commun (Camb) ; 55(91): 13673-13676, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31647081

RESUMO

An array sensing platform exploiting phenyl boronic acid-functionalized pyrene amphiphile/surfactant assemblies is constructed for glycoprotein discrimination, achieving a discrimination sensitivity of 50 nM. Gastric cancer cell lines of various differentiation grades are successfully discriminated, demonstrating its great potential in sensitive differentiation of glycoprotein-related samples in biomedical diagnosis.


Assuntos
Glicoproteínas/análise , Pirenos/química , Tensoativos/química , Ácidos Borônicos/química , Diferenciação Celular , Linhagem Celular Tumoral , Análise Discriminante , Difusão Dinâmica da Luz , Glicoproteínas/urina , Humanos , Micelas , Espectrometria de Fluorescência
2.
Eur J Pharm Biopharm ; 144: 193-206, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31560954

RESUMO

To achieve redox-controlled and tumor active targeting synergistic self-delivery of camptothecin and gemcitabine, redox-sensitive rod-shaped nano-micelles are fabricated through co-assembling between camptothecin-disulfide bond-PEG2000-4-carboxyphenylboronic acid and camptothecin-disulfide bond-gemcitabine conjugate. Most of all, for multidrug resistant cancer cell line MCF-7/ADR which is more resistant against CPT, increasing content of CPT in the formulation is favorable for synergistic effect of CPT and GEM drug combination. Benefiting from simple co-assembling strategy, it is easy and convenient to adjust drug ratio of CPT/GEM to optimize the synergism of drug combination. In addition, nano-micelles fabricated from co-assembling are endowed with both high absolute drug concentration and enhanced colloidal stability, which is helpful to in vivo studies. Transmission electron microscopy observation confirmed the rod-shaped morphology, which is beneficial to cellular internalization, of co-assembled nano-micelles resulting from π-π stacking interactions of CPT moieties and appropriate hydrophilic and hydrophobic interactions during co-assembling. Taking advantages of the specific interactions between 4-carboxyphenylboronic acid and sialic acid, co-assembled nano-micelles exerted enhanced cellular internalization. Noteworthy, compared with cocktail mixture of free CPT and GEM, nano-micelles greatly alleviated drug reflux against MCF-7/ADR and 4T1 cells. The nano-micelles realized redox-controlled ratio-metric and synchronous delivery of CPT and GEM, thereby pronounced in vitro synergistic antiproliferative effect against MCF-7/ADR and 4T1cells. Furthermore, in vivo bio-distribution analysis indicated the preferential accumulation of nano-micelles at tumor site, which could increase therapeutic efficacy and decrease side effects of non-selective anticancer drugs. Taken together, the redox-sensitive CPBA decorated co-assembled nano-micelles provided a promising strategy for tumor active targeting and redox-controlled intracellular synergistic combinational delivery of chemotherapeutics.


Assuntos
Ácidos Borônicos/química , Camptotecina/química , Desoxicitidina/análogos & derivados , Nanopartículas/química , Oxirredução/efeitos dos fármacos , Antineoplásicos/química , Linhagem Celular Tumoral , Desoxicitidina/química , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos/efeitos dos fármacos , Humanos , Interações Hidrofóbicas e Hidrofílicas/efeitos dos fármacos , Células MCF-7 , Micelas , Polietilenoglicóis/química
3.
Chem Soc Rev ; 48(22): 5488-5505, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31552920

RESUMO

Glycans - simple or complex carbohydrates - play key roles as recognition determinants and modulators of numerous physiological and pathological processes. Thus, many biotechnological, diagnostic and therapeutic opportunities abound for molecular recognition entities that can bind glycans with high selectivity and affinity. This review begins with an overview of the current biologically and synthetically derived glycan-binding scaffolds that include antibodies, lectins, aptamers and boronic acid-based entities. It is followed by a more detailed discussion on various aspects of their generation, structure and recognition properties. It serves as the basis for highlighting recent key developments and technical challenges that must be overcome in order to fully deal with the specific recognition of a highly diverse and complex range of glycan structures.


Assuntos
Anticorpos/química , Aptâmeros de Nucleotídeos/química , Ácidos Borônicos/química , Lectinas/química , Polissacarídeos/química , Receptores Artificiais/química , Anticorpos/metabolismo , Aptâmeros de Nucleotídeos/metabolismo , Ácidos Borônicos/metabolismo , Humanos , Lectinas/metabolismo , Polissacarídeos/síntese química , Polissacarídeos/metabolismo , Receptores Artificiais/metabolismo
4.
Nat Protoc ; 14(10): 2972-2985, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31541227

RESUMO

Although Csp2-Csp2 Suzuki-Miyaura couplings (SMCs) are widely used in small-molecule synthesis, related methods that allow the incorporation of Csp3-hybridized coupling partners, particularly in an asymmetric manner, are less developed. This protocol describes catalytic asymmetric SMC reactions that provide access to enantiomerically enriched cyclic allylic products. The method couples racemic allyl halide starting materials with sp2-hybridized boronic acid derivatives and is compatible with heterocyclic coupling partners. These reactions are catalyzed by a rhodium-ligand complex and typically display very high levels of enantioselectivity (>95% enantiomeric excess (ee)). In this protocol, we detail a procedure using a dihydropyridine-derived allyl chloride for the synthesis of (-)-(S)-tert-butyl-3-(4-bromophenyl)-3,6-dihydropyridine-1(2H)-carboxylate, an intermediate in the synthesis of the anticancer drug niraparib. This procedure affords 1.17 g (86% yield) of the coupling product with 96% ee. The initial experimental setup of the reaction takes 45-50 min, and the reaction is complete within 4-5 h.


Assuntos
Ácidos Borônicos/química , Técnicas de Química Sintética/métodos , Ródio/química , Compostos Alílicos/química , Catálise , Indazóis/síntese química , Piperidinas/síntese química , Estereoisomerismo
5.
Int J Nanomedicine ; 14: 6371-6385, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31496692

RESUMO

Background: The phenylboronic acid-functionalized polyamidoamine (PP) was employed as a gene carrier for Dz13 delivery, inducing an obvious anticancer response. Materials and methods: The Dz13 condensation ability of PP was evaluated through gel retardation assay. The cellular uptake mechanism of PP/Dz13 nanoparticles was studied using confocal laser scanning microscope and flow cytometer. The inhibition ability of cell proliferation, migration and invasion was investigated through MTT assay, flow cytometry, wound healing and Transwell migration assays, using hepatocarcinoma cell line HepG2 as a model. Finally, Western blotting analysis was used to detect the signaling pathway associated with the inhibition of cell apoptosis and migration induced by Dz13 delivery. Results: The carrier PP could efficiently condense Dz13 into stable nanoparticles at mass ratios of >1.5. The hydrodynamic diameter and zeta potential of PP/Dz13 nanoparticles were measured to be 204.77 nm and +22.00 mV at a mass ratio of 10.0, respectively. The nanoparticles could realize an efficient cellular uptake in sialic acid-dependent endocytosis manner. Moreover, the nanoparticles exhibited an obvious antiproliferation effect through the induction of cell apoptosis and cell cycle arrest due to the cleavage of c-Jun mRNA. Besides, the suppression of cell migration and invasion could be achieved after the PP/Dz13 transfection, attributing to the decreased expression level of MMP-2 and MMP-9. Conclusion: The PP provided a potential delivery system to achieve the tumor-targeting gene therapy.


Assuntos
Ácidos Borônicos/química , Movimento Celular , DNA Catalítico/administração & dosagem , DNA Catalítico/farmacologia , Poliaminas/química , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Endossomos/efeitos dos fármacos , Endossomos/metabolismo , Células Hep G2 , Humanos , Nanopartículas/química , Nanopartículas/ultraestrutura , Espectroscopia de Prótons por Ressonância Magnética , RNA Mensageiro/genética
6.
Chem Pharm Bull (Tokyo) ; 67(9): 1019-1022, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31474725

RESUMO

A novel catalyst system-a combination of the readily available 2,2'-biphenol with the inexpensive, nontoxic, and eco-friendly B(OH)3-promoted the Nazarov cyclization of activated and inactivated divinyl ketones to afford the corresponding cyclopentenones up to 96% yield under, in a cis-selective manner. Compared with the conventional harsh conditions with hazardous reagents, user-friendly method was established with bench-stable and easy-to-handle reagents.


Assuntos
Fenóis/química , Ácidos Borônicos/química , Catálise , Ciclização , Ciclopentanos/química
7.
Chem Commun (Camb) ; 55(69): 10312-10315, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31397446

RESUMO

Herein, we report a novel magnet-mediated antibody-boronate sandwich-typed assay (ABSTA) strategy for the ultrasensitive, specific, rapid, and enzyme-free detection of glycoproteins in complex samples. The proposed ABSTA method exhibited ultrahigh sensitivity for HCG with a detection limit of 0.19 mIU mL-1, which is approximately 40-fold lower than that of conventional sandwich enzyme immunoassay.


Assuntos
Anticorpos Imobilizados/química , Ácidos Borônicos/química , Gonadotropina Coriônica/sangue , Corantes Fluorescentes/química , Imãs/química , Anticorpos Monoclonais/química , Gonadotropina Coriônica/análise , Fluorescência , Humanos , Imunoensaio/métodos , Limite de Detecção
8.
Chem Commun (Camb) ; 55(71): 10567-10570, 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31417998

RESUMO

Macrocyclization of linear peptide precursors using the Petasis borono-Mannich reaction affords a diverse range of macrocycles with an endocyclic amine. Analysis of the corresponding macrocyclic structures underscores that the hydrogen bond between an endocyclic amine and the adjacent amide NH is a powerful control element for conformationally homogenous peptide macrocycles.


Assuntos
Ácidos Borônicos/química , Compostos Macrocíclicos/síntese química , Peptídeos Cíclicos/síntese química , Aldeídos/química , Amidas/química , Aminas/química , Aziridinas/química , Ciclização
9.
Bioelectrochemistry ; 130: 107344, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31404808

RESUMO

In this work, a novel electrochemical sensing platform was designed and fabricated by the modification of boronic acid functionalized carbon nanodots (B-CNDs) and poly(thionine) (pTHI) on an electrode surface. B-CNDs can not only accelerate electron transfer but also covalently interact with cis-diol groups of dihydronicotinamide adenine dinucleotide (NADH) through functionalized boronic acid groups. Meanwhile, pTHI served as an inner reference element to provide a built-in correction, which enabled the sensor to detect NADH with high accuracy and reliability based on a ratiometric signal (∆INADH/∆ITHI). The electrochemical experimental results demonstrated that the ratiometric strategy-based sensor possessed good selectivity and high sensitivity. A linear range of 5.0 × 10-7 - 2.0 × 10-4 mol/L for NADH detection was obtained with a limit of detection of 1.5 × 10-7 mol/L. The sensor has been applied to analyze NADH in human serum samples with satisfactory results. The simple and effective ratiometric strategy reported here can be further used to prepare electrochemical sensors for selective, sensitive, and reliable detection of other cis-diol compounds.


Assuntos
Ácidos Borônicos/química , Carbono/química , NADP/sangue , Nanoestruturas/química , Fenotiazinas/química , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Eletrodos , Humanos , Limite de Detecção , Polímeros/química , Reprodutibilidade dos Testes
10.
Biomater Sci ; 7(9): 3898-3905, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31317137

RESUMO

To target a response to a high oxidative stress environment of inflammatory or tumor sites, various reactive oxygen species (ROS) sensitive polymers have been developed as drug delivery systems. In this study, a novel oxidation sensitive copolymer, phenylboronic acid pinacol ester-functionalized methoxyl poly(ethylene glycol)-block-poly(phthalic anhydride-alter-glycidyl propargyl ether) (mPEG-b-P(PA-alt-GPBAe)), was designed and synthesized by ring-opening alternating copolymerization (ROAP) and click reaction. The copolymers could self-assemble into micelles in aqueous solution with an average size of 20.3 ± 9.3 nm, and are able to load hydrophobic anticancer drug (doxorubicin, DOX) with a high encapsulation efficiency of 75.2%. Interestingly, the encapsulated drug showed accelerated release in the trigger of H2O2, or at low pH values. The copolymers have low cytotoxicity indicated by the 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay towards 4T1 cells, which showed cell viabilities of more than 80% with treatment of our copolymers at concentrations up to 0.5 mg mL-1. The effective uptake of the drug-loaded micelles by 4T1 cells was investigated by confocal laser scanning microscopy (CLSM) and flow cytometry (FCM) analysis. Finally, compared with free DOX, the DOX-loaded nanoparticles exhibited a better antitumor effect and had lower systemic toxicity in 4T1 tumor-bearing mice. Therefore, this new kind of copolymer acting as a stimuli-responsive nanocarrier should represent a promising therapeutic platform for cancer therapy.


Assuntos
Antineoplásicos/administração & dosagem , Ácidos Borônicos/química , Doxorrubicina/administração & dosagem , Nanocápsulas/química , Polímeros/química , Animais , Linhagem Celular Tumoral , Permeabilidade da Membrana Celular , Sobrevivência Celular/efeitos dos fármacos , Liberação Controlada de Fármacos , Ésteres/química , Humanos , Peróxido de Hidrogênio/metabolismo , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Camundongos , Micelas , Oxirredução , Polietilenoglicóis/química
11.
Chem Commun (Camb) ; 55(62): 9160-9163, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31304937

RESUMO

The rational design of heteroatom-doped C3N4 offers a great opportunity to optimize C3N4 performance. In this communication, we propose a facile method to fabricate layered-stacked B-doped C3N4 (BCN-800) ultrathin nanosheets via a one-step calcination route. The distinctive layered-stacked structure and the presence of B atoms provide an active attachment point for antibodies and antigens. In addition, the presence of C and N might aid stability and increase conductivity. When used for vomitoxin detection, the BCN-800-based electrochemical biosensor exhibits high sensitivity with a detection limit of 0.32 pg mL-1 and superior selectivity to other interfering agents.


Assuntos
Técnicas Biossensoriais , Boro/química , Ácidos Borônicos/química , Contaminação de Alimentos/análise , Inocuidade dos Alimentos/métodos , Nitrilos/síntese química , Tricotecenos/análise , Técnicas Eletroquímicas , Nitrilos/química , Tamanho da Partícula , Propriedades de Superfície
12.
J Sci Food Agric ; 99(14): 6490-6499, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31294828

RESUMO

BACKGROUND: Tropomyosin is now receiving increasing attention because of its significant allergenic activity in various fishery products but its simple and effective isolation still remains a challenging task. RESULTS: An agarose-based boronate affinity chromatography was produced for the first time to isolate tropomyosin in various fishery products using 3,5-difluoro-4-formyl-phenylboronic acid as the functional monomer, tris(2-aminoethyl)amine as the multi-branched ligand, and agarose gel particles as supporting materials. The agarose concentration, binding pH, and the concentration of elution buffers demonstrated significant effects on separation performance. Under optimized conditions, the purity of the isolated tropomyosin was higher than 90%, with the column adsorption capacity over 1.85 mg mL-1 and the enrichment efficiency over 65%. Such efficiency was also validated with different fish samples including Paralichthys olivaceus, Thunnusthynnus, Oreochromis spp., and Lophius litulon. CONCLUSION: In comparison with conventional methods, the established affinity chromatography demonstrated excellent biocompatibility (without involving any organic solvent), better speed (from at least 1-2 days to 3-4 h), and simplicity (from at least five steps to three steps). This suggests that it is a novel and promising technique for the isolation of tropomyosin and other glycoproteins (including most allergens) in foodstuffs. © 2019 Society of Chemical Industry.


Assuntos
Cromatografia de Afinidade/métodos , Proteínas de Peixes/isolamento & purificação , Tropomiosina/isolamento & purificação , Adsorção , Animais , Ácidos Borônicos/química , Cromatografia de Afinidade/instrumentação , Peixes , Sefarose
13.
Chem Commun (Camb) ; 55(64): 9543-9546, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31334509

RESUMO

The novel Vial@FPBA strategy was established for a large-scale pharmacokinetic study of glycosides, during which glycosides were absorbed into a boronic acid-functionalized 96-well glass plate and directly desorbed for UHPLC-MS/MS analysis. Hence, specific and high-throughput glycoside enrichment was achieved simultaneously. The LODs were reduced up to 50 times compared to the case of the methanol method. Meanwhile, sample pre-processing time was greatly saved by skipping the protein sedimentation and supernatant concentration steps.


Assuntos
Ácidos Borônicos/química , Glicosídeos/farmacocinética , Ensaios de Triagem em Larga Escala/métodos , Cromatografia Líquida de Alta Pressão/métodos , Vidro , Limite de Detecção , Espectrometria de Massas em Tandem/métodos
14.
J Chromatogr A ; 1602: 91-99, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31229248

RESUMO

Endotoxins are found almost everywhere and possess high toxicity in vivo and in vitro. Here we design a novel boronate affinity material, called boronic acid-functionalized mesoporous silica-coated core/shell magnetic microspheres (Fe3O4@nSiO2@mSiO2-BA) with large pores (pore size > 20 nm) based on the chemical structure and physical properties of endotoxins, for facile and highly efficient removal of endotoxins. Dual modes for endotoxin removal were proposed and confirmed in this work: the endotoxin aggregates with size < 20 nm were bound with boronic acid ligands chemically modified on the inner and outer surface of the large pores of Fe3O4@nSiO2@mSiO2-BA microspheres; while the larger endotoxin micelles (size >20 nm) were absorbed on the outer surface of the prepared material based on boronate affinity. Transmission electron microscopy (TEM), X-ray diffraction (XRD), nitrogen adsorption/desorption isotherms and Fourier transform infrared (FT-IR) spectroscopy confirm that Fe3O4@nSiO2@mSiO2-BA microspheres possess core/shell structure, uniform diameter (520 nm), high surface area (205.57 m2/g), large mesopores (21.8 nm) and boronic acid ligands. The purification procedures of Fe3O4@nSiO2@mSiO2-BA microspheres for endotoxin were optimized, and 50 mM NH4HCO3 (pH 8.0) and 0.05 M fructose were selected as loading/washing, elution buffers, respectively. The binding capacity of Fe3O4@nSiO2@mSiO2-BA microspheres for endotoxin was calculated to be 60.84 EU/g under the optimized conditions. Finally, the established analytical method was applied to remove endotoxins from plasmid DNA. After endotoxin removal, the endotoxin content in plasmid DNA was reduced from 0.0026 to 0.0006 EU/mL for two-fold concentration, and from 0.0088 to 0.0022 EU/mL for five-fold concentration after binding, respectively. Additional advantages of the prepared boronate affinity material include excellent stability, reusability/repeatability, and low cost. Boronate affinity materials with large pores could thus prove to be powerful adsorbents for endotoxin removal and the potential applications in the aspects of biological research, pharmaceutical industry, and life health.


Assuntos
Ácidos Borônicos/química , Endotoxinas/isolamento & purificação , Magnetismo , Microesferas , Dióxido de Silício/química , Adsorção , Tampões (Química) , Compostos Férricos/química , Porosidade , Padrões de Referência , Difração de Raios X
16.
Chemistry ; 25(42): 9834-9839, 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31173417

RESUMO

Introduction of chirality into a supramolecular self-assembly system plays an indispensable role in attaining specific molecular recognition ability. Herein, a chiral anticancer drug 5'-deoxy-5-fluorouridine (5'DFU) was explored for inducing the self-assembly of a cationic perylene diimide derivative containing boronic acid groups (PDI-PBA) into a highly ordered right-handed helical structure. As a result, PDI-PBA exhibited a molecular recognition ability towards 5'DFU among other cis-diols and anticancer drugs. With the help of a dynamic covalent bond and favorable hydrogen-bonding interactions, chirality transfer from chiral 5'DFU to achiral PDI-PBA breaks down the strong π-π stacking of PDI-PBA and makes it reorganize into highly ordered helical supramolecular structures. This work provides an insight into chiral anticancer drug tuning interactions of π-chromophores and the inducement of hierarchical self-assembly to achieve specific molecular recognition.


Assuntos
Antineoplásicos/química , Corantes Fluorescentes/química , Imidas/química , Perileno/análogos & derivados , Ácidos Borônicos/química , Ligações de Hidrogênio , Modelos Moleculares , Conformação Molecular , Perileno/química , Espectrometria de Fluorescência , Estereoisomerismo , Termodinâmica
17.
Adv Mater ; 31(32): e1902542, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31183900

RESUMO

Current cancer immunotherapies including chimeric antigen receptor (CAR)-based therapies and checkpoint immune inhibitors have demonstrated significant clinical success, but always suffer from immunotoxicity and autoimmune disease. Recently, nanomaterial-based immunotherapies are developed to precisely control in vivo immune activation in tumor tissues for reducing immune-related adverse events. However, little consideration has been put on the spatial modulation of interactions between immune cells and cancer cells to optimize the efficacy of cancer immunotherapies. Herein, a rational design of immunomodulating nanoparticles is demonstrated that can in situ modify the tumor cell surface with natural killer cell (NK cell)-activating signals to achieve in situ activation of tumor-infiltrating NK cells, as well as direction of their antitumor immunity toward tumor cells. Using these immunomodulating nanoparticles, the remarkable inhibition of tumor growth is observed in mice without noticeable side effects. This study provides an accurate immunomodulation strategy that achieves safe and effective antitumor immunity through in situ NK cell activation in tumors. Further development by constructing interactions with various immune cells can potentially make this nanotechnology become a general platform for the design of advanced immunotherapies for cancer treatments.


Assuntos
Membrana Celular/imunologia , Fatores Imunológicos/química , Células Matadoras Naturais/metabolismo , Nanopartículas/química , Resinas Acrílicas/química , Animais , Ácidos Borônicos/química , Linhagem Celular Tumoral , Reagentes para Ligações Cruzadas/química , Portadores de Fármacos/química , Imunoglobulina G/química , Imunoterapia , Células Matadoras Naturais/imunologia , Camundongos , Transplante de Neoplasias , Polímeros/química , Soroalbumina Bovina/química , Propriedades de Superfície
18.
J Nanobiotechnology ; 17(1): 74, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31159842

RESUMO

BACKGROUND: Diabetes is one of the biggest medical challenges worldwide. The key to efficiently treat type 1 diabetes is to accurately inject insulin according to the blood glucose levels. In this study, we aimed to develop an intelligent insulin-releasing gold nanocluster system that responds to environmental glucose concentrations. RESULTS: We employed gold nanoclusters (AuNCs) as a novel carrier nanomaterial by taking advantage of their high drug-loading capacity. We prepared AuNCs in the protection of bovine serum albumin, and we decorated AuNCs with 3-aminophenylboronic acid (PBA) as a glucose-responsive factor. Then we grafted insulin onto the surface to obtain the glucose-responsive insulin-releasing system, AuNC-PBA-Ins complex. The AuNC-PBA-Ins complex exhibited high sensitivity to glucose concentration, and rapidly released insulin in high glucose concentration in vitro. In the type 1 diabetic mouse model in vivo, the AuNC-PBA-Ins complex effectively released insulin and regulated blood glucose level in the normoglycemic state for up to 3 days. CONCLUSIONS: We successfully developed a phenylboronic acid-functionalized gold nanocluster system (AuNC-PBA-Ins) for responsive insulin release and glucose regulation in type 1 diabetes. This nanocluster system mimics the function of blood glucose regulation of pancreas in the body and may have potential applications in the theranostics of diabetes.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Ouro/química , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Nanopartículas Metálicas/química , Animais , Glicemia/análise , Ácidos Borônicos/química , Bovinos , Hipoglicemiantes/química , Insulina/química , Masculino , Camundongos Endogâmicos C57BL , Soroalbumina Bovina/química
19.
Chem Soc Rev ; 48(13): 3513-3536, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31157810

RESUMO

Bioconjugates are multifunctional constructs in which biomolecules like peptides, proteins, vitamins and nucleic acids are endowed with the properties of specific payloads. These constructs recently emerged as a new generation of high-precision therapeutics, with several representatives reaching the market. This success stimulated an intense search for new biocompatible synthetic methodologies to connect both components and to control the bioconjugate's function. Despite the remarkable advances made in this field, most of the technologies developed for the construction of bioconjugates were engineered to yield stable constructs that can endure complex physiological conditions. Because of this, the use of reversible covalent bonds in the synthesis of bioconjugates has been rather overlooked, notwithstanding the potential of this strategy to generate stimuli responsive constructs that may operate in areas like the selective delivery of drugs, live-cell imaging and new theranostic approaches. Boronic acids are a well-known class of reagents that have been widely used in modern synthesis for the formation of C-C and C-heteroatom bonds. Apart from this, boronic acids exhibit an exquisite reversible coordination profile that can be explored as a molecular construction tool featuring specific mechanisms to control the structure and biological properties of bioconjugates. In this review, the use of boronic acids in the construction of therapeutically useful bioconjugates will be discussed, focusing on the molecular mechanisms that allow the use of these reagents as bioconjugation warheads, as central pieces of linker structures and as functional payloads.


Assuntos
Materiais Biocompatíveis/química , Ácidos Borônicos/química , Animais , Materiais Biocompatíveis/uso terapêutico , Ácidos Borônicos/uso terapêutico , Sistemas de Liberação de Medicamentos , Desenho de Drogas , Humanos , Nanomedicina Teranóstica
20.
Analyst ; 144(11): 3643-3648, 2019 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-31073567

RESUMO

Using fluorescent probes to detect endogenous hydrogen peroxide, which is associated with many diseases in the human body, remains an essential technique. Cyanine fluorochromes are a class of dyes that have attracted much attention and are widely used in the synthesis of fluorescent probes. In this article, a novel near-infrared (NIR) fluorescence probe for the detection of hydrogen peroxide was constructed and successfully applied to imaging endogenous hydrogen peroxide in vivo. Notably, probe 1 was designed by connecting 4-(bromomethyl)benzeneboronic acid pinacol ester as the sensing unit to the IR-780 hemicyanine skeleton, which exhibits excellent properties like NIR fluorescence emission over 700 nm. Probe 1 has satisfactory sensitivity to hydrogen peroxide with a low detection limit of 0.14 µM (S/N = 3), attributed to a responding mechanism that leads to the oxidation of phenylboronic acid pinacol ester and thereby releases fluorophore 2. Moreover, probe 1 displays excellent selectivity towards hydrogen peroxide over other substances. Taking advantage of these properties, the probe proved to be cell-permeable. Based on the results of N-acetylcysteine and rotenone together, probe 1 is capable of clearly visualizing endogenously produced hydrogen peroxide in living HepG2 cells and mice. The superior performance of the probe, as a reliable chemical tool, makes it of great potential application for exploring the role played by hydrogen peroxide in biological systems.


Assuntos
Ácidos Borônicos/química , Corantes Fluorescentes/química , Peróxido de Hidrogênio/análise , Indóis/química , Acetilcisteína/farmacologia , Animais , Antioxidantes/farmacologia , Ácidos Borônicos/síntese química , Ácidos Borônicos/toxicidade , Fluorescência , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/toxicidade , Células Hep G2 , Humanos , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/metabolismo , Concentração de Íons de Hidrogênio , Indóis/síntese química , Indóis/toxicidade , Limite de Detecção , Camundongos Endogâmicos BALB C , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos , Oxirredução , Rotenona/farmacologia , Temperatura Ambiente
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