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1.
Int J Nanomedicine ; 15: 5433-5443, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32801698

RESUMO

Background: Human epidermal growth factor receptor2 (Her2) positive breast cancer represents 25% of breast cancer cases. Targeted therapy with Her2 monoclonal antibody, trastuzumab (TZ), represents the first-line treatment for this type of breast cancer. In addition, neratinib, an irreversible inhibitor of the HER-2 receptor tyrosine kinase, has recently been approved as adjuvant therapy to TZ. This study aims to formulate (TZ)-grafted dendrimers loaded with neratinib, allowing a dual treatment alongside reducing the associated resistance as well as targeted therapy. Methods: TZ was conjugated on the surface of dendrimer using hetero-cross linker, MAL-PEG-NHS, and the zeta potential, and in vitro release of neratinib from dendrimers was characterized. Formulated dendrimers were also fluorescently conjugated with fluorescein isothiocyanate to visualize and quantify their SKBR-3 cellular uptake. Results: The G4 PAMAM dendrimer showed successful encapsulation of neratinib and a sustained release profile. Comparative in vitro studies revealed that these TZ-targeted dendrimers loaded with neratinib were more selective and have higher antiproliferation activity against SKBR-3 cells compared to neratinib alone and neratinib loaded dendrimer. Conclusion: In the current study, neratinib loaded in plain and trastuzumab-grafted dendrimer were successfully prepared. Enhanced cellular uptake of trastuzumab conjugated dendrimers was shown, together with a higher cytotoxic effect than plain neratinib dendrimers. These findings suggest the potential of TZ-conjugated dendrimers as targeting carrier for cytotoxic drugs, including neratinib.


Assuntos
Dendrímeros/química , Nanocápsulas/administração & dosagem , Nylons/química , Quinolinas/química , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Dendrímeros/administração & dosagem , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Feminino , Fluoresceína-5-Isotiocianato , Humanos , Terapia de Alvo Molecular/métodos , Nanocápsulas/química , Poliaminas/química , Quinolinas/administração & dosagem , Quinolinas/farmacocinética , Receptor ErbB-2/antagonistas & inibidores , Trastuzumab/administração & dosagem , Trastuzumab/química , Trastuzumab/farmacocinética
2.
Int J Nanomedicine ; 15: 2633-2646, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32368045

RESUMO

Objective: The aim of this study is to fabricate functional scaffolds to gene delivery bone morphogenetic protein-2 (BMP-2) plasmid for bone formation in bone tissue engineering. Methods: Dendriplexes (DPs) of generation 4 polyamidoamin (G4-PAMAM)/BMP-2 plasmid were prepared through microfluidic (MF) platform. The physiochemical properties and toxicity of DPs were evaluated by DLS, AFM, FESEM and MTT assay. In order to create a suitable environment for stem cell growth and differentiation, poly-l-lactic acid (PLLA) and poly-l-lactic acid/poly (ethylene oxide) (PLLA/PEO) scaffolds containing hydroxyapatite nanoparticles (HA) and DPs were fabricated by the electrospinning method. The osteogenic potency of the scaffolds on human adipose tissue-derived mesenchymal stem cells (hASCs) was investigated. Results: The results revealed that tuning the physical properties of DPs by adjusting flow parameters in microfluidic platform can easily improve the cell viability compared to conventional bulk mixing method. Also, the result showed that the presence of HA and DPs in PLLA/PEO scaffold enhanced alkaline phosphatase (ALP) activity and increased the amount of deposited Ca, as well as, related to osteogenesis gen markers. Conclusion: This study indicated that on using the MF platform in preparation of DPs and loading them along with HA in PLLA/PEO scaffold, the osteogenic differentiation of hASCs could be tuned.


Assuntos
Proteína Morfogenética Óssea 2/metabolismo , Osso e Ossos/fisiologia , Durapatita/química , Microfluídica , Nanofibras/química , Poliaminas/química , Engenharia Tecidual/métodos , Tecidos Suporte/química , Fosfatase Alcalina/metabolismo , Cálcio/metabolismo , Adesão Celular , Morte Celular , Diferenciação Celular , Proliferação de Células , Forma Celular , DNA/metabolismo , Dendrímeros/química , Humanos , Células-Tronco Mesenquimais/metabolismo , Nanopartículas/química , Tamanho da Partícula , Plasmídeos/metabolismo , Poliésteres/química , Resistência à Tração
3.
Inorg Chem ; 59(12): 8308-8319, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32437613

RESUMO

Despite a comprehensive study on the biosynthesis and function of nitric oxide, biological metabolism of nitric oxide, especially when its concentration exceeds the cytotoxic level, remains elusive. Oxidation of nitric oxide by O2 in aqueous solution has been known to yield NO2-. On the other hand, a biomimetic study on the metal-mediated conversion of NO to NO2-/NO3- via O2 reactivity disclosed a conceivable pathway for aerobic metabolism of NO. During the NO-to-NO3- conversion, transient formation of metal-bound peroxynitrite and subsequent release of •NO2 via O-O bond cleavage were evidenced by nitration of tyrosine residue or 2,4-di-tert-butylphenol (DTBP). However, the synthetic/catalytic/enzymatic cycle for conversion of nitric oxide into a nitrite pool is not reported. In this study, sequential reaction of the ferrous complex [(PMDTA)Fe(κ2-O,O'-NO2)(κ1-O-NO2)] (3; PMDTA = pentamethyldiethylenetriamine) with NO(g), KC8, and O2 established a synthetic cycle, complex 3 → {Fe(NO)2}9 DNIC [(PMDTA)Fe(NO)2][NO2] (4) → {Fe(NO)2}10 DNIC [(PMDTA)Fe(NO)2] (1) → [(PMDTA)(NO)Fe(κ2-O,N-ONOO)] (2) → complex 3, for the transformation of nitric oxide into nitrite. In contrast to the reported reactivity of metal-bound peroxynitrite toward nitration of DTBP, peroxynitrite-bound MNIC 2 lacks phenol nitration reactivity toward DTBP. Presumably, the [(PMDTA)Fe] core in {Fe(NO)}8 MNIC 2 provides a mononuclear template for intramolecular interaction between Fe-bound peroxynitrite and Fe-bound NO-, yielding Fe-bound nitrite stabilized in the form of complex 3. This [(PMDTA)Fe]-core-mediated concerted peroxynitrite homolytic O-O bond cleavage and combination of the O atom with Fe-bound NO- reveals a novel and effective pathway for NO-to-NO2- transformation. Regarding the reported assembly of the dinitrosyliron unit (DNIU) [Fe(NO)2] in the biological system, this synthetic cycle highlights DNIU as a potential intermediate for nitric oxide monooxygenation activity in a nonheme iron system.


Assuntos
Complexos de Coordenação/química , Compostos Férricos/química , Compostos Ferrosos/química , Óxido Nítrico/química , Nitritos/química , Poliaminas/química , Complexos de Coordenação/síntese química , Estrutura Molecular , Oxigênio/química
4.
Int J Nanomedicine ; 15: 1611-1622, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32210555

RESUMO

Purpose: Quantum dots (QDs) are used as fluorescent probes due to their high fluorescence intensity, longevity of fluorescence, strong light-resistant bleaching ability and high light stability. Therefore, we explore a more precise probe that can target an organelle. Methods: In the current study, a new class of fluorescence probes were developed using QDs capped with 4 different L-cysteine-polyamine-morpholine linked by mercapto groups. Ligands were characterised by Electrospray ionization mass spectrometry (ESI-MS), H-Nuclear Magnetic Resonance (1H NMR) spectroscopy, and 13C NMR spectroscopy. Modified QDs were characterized by Transmission Electron Microscope (TEM), Ultraviolet and visible spectrophotometry (UV-Vis), and fluorescence microscopy. And the biological activity of modified QDs was explored by using MTT assay with HeLa, SMMC-7721 and HepG2 cells. The fluorescence imaging of modified QDs was obtained by confocal laser scanning fluorescence microscopy (CLSM). Results: Synthesized QDs ranged between 4 to 5 nm and had strong optical emission properties. UV-Vis and fluorescence spectra demonstrated that the cysteine-polyamine-morpholine were successfully incorporated into QD nanoparticles. The MTT results demonstrated that modified QDs had lesser cytotoxicity when compared to unmodified QDs. In addition, modified QDs had strong fluorescence intensity in HeLa cells and targeted lysosomes of HeLa cells. Conclusion: This study demonstrates the modified QDs efficiently entered cells and could be used as a potential lysosome-targeting fluorescent probe.


Assuntos
Corantes Fluorescentes/química , Lisossomos/efeitos dos fármacos , Microscopia Confocal/métodos , Pontos Quânticos/química , Cisteína/química , Corantes Fluorescentes/análise , Células HeLa , Células Hep G2 , Humanos , Microscopia de Fluorescência , Morfolinas/química , Nanopartículas/química , Poliaminas/química , Pontos Quânticos/análise , Solubilidade , Espectrofotometria Ultravioleta
5.
Nat Microbiol ; 5(4): 554-561, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32094585

RESUMO

Polyamines are essential metabolites that play an important role in cell growth, stress adaptation and microbial virulence1-3. To survive and multiply within a human host, pathogenic bacteria adjust the expression and activity of polyamine biosynthetic enzymes in response to different environmental stresses and metabolic cues2. Here, we show that ornithine capture by the ribosome and the nascent peptide SpeFL controls polyamine synthesis in γ-proteobacteria by inducing the expression of the ornithine decarboxylase SpeF4, via a mechanism involving ribosome stalling and transcription antitermination. In addition, we present the cryogenic electron microscopy structure of an Escherichia coli ribosome stalled during translation of speFL in the presence of ornithine. The structure shows how the ribosome and the SpeFL sensor domain form a highly selective binding pocket that accommodates a single ornithine molecule but excludes near-cognate ligands. Ornithine pre-associates with the ribosome and is then held in place by the sensor domain, leading to the compaction of the SpeFL effector domain and blocking the action of release factor 1. Thus, our study not only reveals basic strategies by which nascent peptides assist the ribosome in detecting a specific metabolite, but also provides a framework for assessing how ornithine promotes virulence in several human pathogens.


Assuntos
Proteínas de Bactérias/química , Escherichia coli/genética , Ornitina Descarboxilase/química , Ornitina/química , Ribossomos/química , Sequência de Aminoácidos , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Sequência de Bases , Sítios de Ligação , Enterococcus faecalis/genética , Enterococcus faecalis/metabolismo , Escherichia coli/metabolismo , Escherichia coli/patogenicidade , Modelos Moleculares , Ornitina/metabolismo , Ornitina Descarboxilase/genética , Ornitina Descarboxilase/metabolismo , Fatores de Terminação de Peptídeos/química , Fatores de Terminação de Peptídeos/genética , Fatores de Terminação de Peptídeos/metabolismo , Filogenia , Poliaminas/química , Poliaminas/metabolismo , Ligação Proteica , Biossíntese de Proteínas , Domínios e Motivos de Interação entre Proteínas , RNA de Transferência/química , RNA de Transferência/genética , RNA de Transferência/metabolismo , Ribossomos/metabolismo , Salmonella typhimurium/genética , Salmonella typhimurium/metabolismo , Salmonella typhimurium/patogenicidade , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Thermus thermophilus/genética , Thermus thermophilus/metabolismo , Virulência
6.
World J Microbiol Biotechnol ; 36(3): 38, 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32095897

RESUMO

Biorecovery is emerging as a promising approach to retrieve gold from various sources, while its efficiency is usually restricted by the limited functional groups on natural microbial biomass surface. This study aims to intensify Pycnoporus sanguineus boosted sorption-reduction coupled gold biorecovery process via microbial surface modification. Results showed that grafting polyallylamine hydrochloride onto P. sanguineus biomass surface increased amino group content on microbial biomass surface from 1.29 to 2.81 mmol/g. When applying modified biomass to gold biorecovery with initial gold concentrations of 1.0, 2.0 and 3.0 mM, biosorption equilibrium time shortened to the 12.5%, 37.5% and 41.7% of those obtained with pristine biomass, and sorption rate constants correspondingly increased to 11.2, 3.1 and 3.7 folds as well. Maximum sorption capacity increased 30% and the affinity between biomass and gold enhanced heavily after microbial surface modification. Meanwhile, microbial surface modification favored gold reduction and gold nanoparticles (AuNPs) formation. The change of microbial biomass morphology from smooth surface with some branched structure to layered stacking structure with many pores and the increase of amino group content on microbial biomass surface were the main impetus for the gold bioreocovery process intensification.


Assuntos
Ouro/química , Poliaminas/química , Pycnoporus/crescimento & desenvolvimento , Adsorção , Biodegradação Ambiental , Biomassa , Nanopartículas Metálicas , Espectroscopia Fotoeletrônica , Propriedades de Superfície , Difração de Raios X
7.
Carbohydr Polym ; 234: 115928, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32070544

RESUMO

We developed a co-delivery system of nitric oxide (NO) and antibiotic for the antibiotic-resistant bacterial infection therapy. The NO could disperse the bacterial biofilms and convert the bacteria into an antibiotic-susceptible planktonic form. Using the chitosan-graft-poly(amidoamine) dendrimer (CS-PAMAM) as the co-delivery system, methicillin (MET) and NO were conjugated successively to form CS-PAMAM-MET/NONOate. The positive CS-PAMAM could efficiently capture the negatively charged bacteria and PAMAM provide abundant reaction points for high payloads of NO and MET. The CS-PAMAM-MET/NONOate displayed effective and combined antibacterial activity to the E. coli and S. aureus. Particularly, for the MET-resistant S. aureus (MRSA), the CS-PAMAM-MET/NONOate displayed the synergistic antibacterial activity. In vivo wound healing assays also confirmed that CS-PAMAM-MET/NONOate could heal the infection formed by MRSA and then accelerate the wound healing effectively. Moreover, CS-PAMAM-MET/NONOate showed no toxicity towards 3T3 cells in vitro and rats in vivo, providing a readily but high-efficient strategy to drug-resistant bacterial infection therapy.


Assuntos
Antibacterianos/farmacologia , Quitosana/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Meticilina/farmacologia , Óxido Nítrico/farmacologia , Infecções Estafilocócicas/tratamento farmacológico , Animais , Antibacterianos/síntese química , Antibacterianos/química , Biofilmes/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Quitosana/química , Dendrímeros/química , Dendrímeros/farmacologia , Sistemas de Liberação de Medicamentos , Masculino , Meticilina/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Óxido Nítrico/análise , Óxido Nítrico/metabolismo , Tamanho da Partícula , Poliaminas/química , Poliaminas/farmacologia , Ratos , Ratos Sprague-Dawley , Infecções Estafilocócicas/patologia , Propriedades de Superfície
9.
Int J Nanomedicine ; 15: 227-238, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32021176

RESUMO

Introduction: Multimodal imaging agent has the potential to overcome the shortage and incorporate the advantages of different imaging tools for extremely sensitive diagnosis. To achieve multimodal imaging, combining multiple contrast agents into a special nanostructure has become a main strategy; However, the combination of all of these functions into one nanoplatform usually requires a complicated synthetic procedure that results in heterogeneous nanostructure. Methods: In this study, we develop ultrasmall gold nanoclusters with 15 gold atoms (Au15NCs) functionalized with diethylenetriamine-pentaacetic acid dianhydride (DTPAA-Gd) as an optimized multimodal imaging agent to enhance imaging ability. Results: The Au15NCs-DTPAA-Gd nanohybrids possess the ultra-small size and are capable of enhancing the contrast in near-infrared fluorescence (NIRF), magnetic resonance (MR) and X-ray computed tomography (CT) imaging. Meanwhile, the integrated DTPAA-Gd component not only endow the nanohybrids to produce higher T1 relaxivity (r1 = 21.4 mM-1 s-1) than Omnipaque (r1 = 3.973 mM-1s-1) but also further enhance X-ray attenuation property of Au15NCs. Importantly, the fluorescence intensity of Au15NCs-DTPAA-Gd did not decrease compared with Au15NCs. Ultimately, in vivo imaging experiments have demonstrated that Au15NCs-DTPAA-Gd nanohybrids can be quickly eliminated from the body through the urinary system and has great potential for anatomical imaging. Conclusion: These data manifest Au15NCs-DTPAA-Gd present great potential as a multimodal contrast agent for disease diagnosis, especially for early accurate detection of tumors.


Assuntos
Anidridos/química , Meios de Contraste/química , Ouro/química , Imagem Multimodal/métodos , Nanocompostos/química , Ácido Pentético/química , Anidridos/farmacocinética , Animais , Meios de Contraste/farmacocinética , Fluorescência , Gadolínio/química , Células HEK293 , Células Hep G2 , Humanos , Imagem por Ressonância Magnética/métodos , Camundongos Endogâmicos BALB C , Ácido Pentético/farmacocinética , Poliaminas/química , Espectroscopia de Luz Próxima ao Infravermelho , Distribuição Tecidual , Tomografia Computadorizada por Raios X/métodos
10.
Chemistry ; 26(11): 2456-2463, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-31889346

RESUMO

Polyamine-salt aggregates (PSA) are biomimetic soft materials that have attracted great attention due to their straightforward fabrication methods, high drug-loading efficiencies, and attractive properties for pH-triggered release. Herein, a simple and fast multicomponent self-assembly process was used to construct cross-linked poly(allylamine hydrochloride)/phosphate PSAs (hydrodynamic diameter of 360 nm) containing glucose oxidase enzyme, as a glucose-responsive element, and human recombinant insulin, as a therapeutic agent for the treatment of diabetes mellitus (GI-PSA). The addition of increasing glucose concentrations promotes the release of insulin due to the disassembly of the GI-PSAs triggered by the catalytic in situ formation of gluconic acid. Under normoglycemia, the GI-PSA integrity remained intact for at least 24 h, whereas hyperglycemic conditions resulted in 100 % cargo release after 4 h of glucose addition. This entirely supramolecular strategy presents great potential for the construction of smart glucose-responsive delivery nanocarriers.


Assuntos
Sistemas de Liberação de Medicamentos , Glucose/química , Insulina/administração & dosagem , Insulina/química , Nanocápsulas/química , Poliaminas/química , Reagentes para Ligações Cruzadas/química , Diabetes Mellitus/tratamento farmacológico , Gluconatos/química , Humanos , Insulina/farmacologia
11.
Anal Bioanal Chem ; 412(6): 1353-1363, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31900540

RESUMO

The study of biologically important Cu2+ and S2- ions has drawn great attention in the recent years since an abnormal level of these ions is an indication for health impairment. Therefore, a reliable strategy for effective fluorescence determination of Cu2+ and S2- ions was developed. Simply, the method based on economical plant-dependent thermolysis procedure for efficient green synthesis of water dispersible luminescent polyamine-based carbon dots (PA@C-dots) utilizes Vitis vinifera juice as precursor with a high quantum yield (32.1%) and good photo-stability. The fluorescent PA@C-dots were characterized by different spectroscopical, physical, and structural techniques. Furthermore, the synthesized PA@C-dots can be used as an efficient dual functional fluorescent probe for the sensitive and selective estimation of Cu2+ and S2- ions. The incorporation of Cu2+ ions and their adsorption on the surface of PA@C-dot skeleton leads to the respectable fluorescence quenching of C-dots (turn-off mode). The Cu2+-PA@C-dot was found to be sensitive to S2- ions. The addition of S2- recovers the fluorescence (turn-on mode) of Cu2+-PA@C-dots, thanks to its capacity for withdrawing Cu2+ from the shell of PA@C-dots. Fluorescence quenching in the range of 0.07-60 µM Cu2+ was obtained with LOD and LOQ of 0.02 and 0.066 µM, respectively. Sulfide detection provides linearity in the range of 0.8 to 95 µM with LOD and LOQ of 0.24 and 0.79 µM, respectively. The optimal excitation and emission wavelengths for all experiments are 435 nm and 498 nm, respectively. Experiment results elucidate that the proposed method is suitable for Cu2+and S2- ion detection in environmental water samples. Graphical abstract Green synthesis of polyamine-functionalized nanoprobe by thermolysis method from plant source as bifunctional sensing platform for determination of Cu2+ and S2- in environmental water samples.


Assuntos
Carbono/química , Cobre/análise , Química Verde , Poliaminas/química , Pontos Quânticos/química , Enxofre/análise , Limite de Detecção , Microscopia Eletrônica de Transmissão , Difração de Pó , Análise Espectral/métodos , Vitis/química
12.
Mater Sci Eng C Mater Biol Appl ; 108: 110369, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31923961

RESUMO

Bionanocomposite materials were developed from the assembly of polymer-coated copper-cystine high-aspect ratio structures (CuHARS) and cellulose fibers. The coating of the metal-organic materials with polyallylamine hydrochloride (PAH) allows their covalent linkage to TEMPO-oxidized cellulose by means of EDC/NHS. The resulting materials can be processed as films or macroporous foams by solvent casting and lyophilization, respectively. The films show good mechanical behavior with Young's moduli around 1.5 GPa as well as resistance in water, while the obtained foams show an open network of interconnected macropores with average diameters around 130 µm, depending on the concentration of the initial suspension, and compression modulus values around 450 kPa, similar to other reported freeze-dried nanocellulose-based aerogels. Based on these characteristics, the cellulose/PAH-CuHARS composites are promising for potential biomedical applications as implants or wound dressing materials. They have proved to be effective in the decomposition of low molecular weight S-nitrosothiols (RSNOs), similar to those existing in blood, releasing nitric oxide (NO). This effect is attributed to the presence of copper in the crystalline structure of the CuHARS building unit, which can be gradually released in the presence of redox species like ascorbic acid, typically found in blood. The resulting biomaterials can offer the interesting properties associated with NO, like antimicrobial activity as preliminary tests showed here with Escherichia coli and Staphylococcus epidermidis. In the presence of physiological concentration of RSNOs the amount of generated NO (around 360 nM) is not enough to show bactericidal effect on the studied bacteria, but it could provide other properties inherent to NO even at low concentration in the nM range like anti-inflammatory and anti-thrombotic effects. The cytotoxic effect recorded of the films on rat brain endothelial cells (BMVECs) is least significant and proves them to be friendly enough for further biological studies.


Assuntos
Materiais Biocompatíveis/química , Celulose/química , Cobre/química , Cistina/química , Óxido Nítrico/análise , Animais , Encéfalo/irrigação sanguínea , Catálise , Sobrevivência Celular/efeitos dos fármacos , Celulose/ultraestrutura , Contagem de Colônia Microbiana , Cisteína/análogos & derivados , Cisteína/análise , Módulo de Elasticidade , Células Endoteliais/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Cinética , Microvasos/citologia , Poliaminas/química , Porosidade , Ratos , S-Nitrosotióis/análise , Espectroscopia de Infravermelho com Transformada de Fourier , Staphylococcus epidermidis/efeitos dos fármacos , Staphylococcus epidermidis/crescimento & desenvolvimento
13.
Mater Sci Eng C Mater Biol Appl ; 108: 110424, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31923979

RESUMO

Fluorescent hydroxyapatite (HAp) nanoparticles have received significant attention in biomedical fields due to their outstanding advantages, such as low immunogenicity, excellent biocompatibility and biodegradability. However, fluorescent HAp nanoparticles with well controlled size and morphology are coated with hydrophobic molecules and their biomedical applications are largely restricted by their poor dispersibility in physiological solutions. Therefore, surface modification of these hydrophobic fluorescent HAp nanoparticles to render them water dispersibility is of utmost importance for biomedical applications. In this work, we reported for the first time for preparation of water-dispersible hydrophilic fluorescent Eu3+-doped HAp nanoparticles (named as HAp-PEOTx) through the cationic ring-opening polymerization using hydrophilic and biocompatible 2-ethyl-2-oxazoline (EOTx) as the monomer. The characterization techniques, such as nuclear magnetic resonance (NMR) spectroscopy, transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS) have been used to characterize these samples. Results confirmed that we could successfully obtain the hydrophilic fluorescent HAp-PEOTx composites through the strategy described above. These fluorescent HAp-PEOTx composites display great water dispersibility, unique fluorescent properties and excellent biocompatibility, making them promising for in vitro bioimaging applications.


Assuntos
Durapatita/química , Nanopartículas/química , Poliaminas/química , Polimerização
14.
Biosens Bioelectron ; 153: 112029, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31989938

RESUMO

In the current study, we report on the design and development of a novel electrochemical immunosensor for the detection of cancer antigen 125 (CA125) oncomarker. Polyamidoamine/gold nanoparticles (PAMAM/AuNPs) were used to increase the conductivity and enhance the number of antibodies (Abs) immobilized on the electrode surface. Three-dimensional reduced graphene oxide-multiwall carbon nanotubes (3DrGO-MWCNTs) were used to modify the glassy carbon electrode to improve the electrode conductivity and specific surface area. Ab and toluidine blue attached to O-succinyl-chitosan-magnetic nanoparticles (Suc-CS@MNPs) as a tracer. The poor solubility of chitosan (CS) was improved by succinic anhydride using a novel modification method. Under optimum condition, the developed immunosensor exhibited a wide linear range (0.0005-75 U/mL) and an excellent limit of detection around 6 µU/mL. The reliability of the engineered immunosensor in detecting CA125 was verified by standard addition recovery method, which was further compared to enzyme-linked immunosorbent assay (ELISA). The proposed immunosensor exhibited excellent stability, high selectivity and sensitivity, and good reproducibility. Based on the great performance of the engineered immunosensor, it is proposed as a robust and reliable diagnostic tool for the detection of CA125 in the clinic.


Assuntos
Biomarcadores Tumorais/análise , Antígeno Ca-125/análise , Técnicas Eletroquímicas/métodos , Proteínas de Membrana/análise , Neoplasias Ovarianas/diagnóstico , Anticorpos Imobilizados/química , Técnicas Biossensoriais , Quitosana/química , Condutividade Elétrica , Eletrodos , Feminino , Ouro/química , Grafite/química , Humanos , Imunoensaio , Limite de Detecção , Nanopartículas Metálicas/química , Nanotubos de Carbono/química , Poliaminas/química , Propriedades de Superfície
15.
Drug Dev Ind Pharm ; 46(2): 283-295, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31944130

RESUMO

In this study, we evaluated and screened the effects of the molecular weight (MW) and molar ratio of poly(2-ethyl-2-oxazoline)-cholesteryl methyl carbonate (PEtOz-CHMC) on the pH sensitivity, stability, and antitumor efficacy of liposomes. The pH sensitivity of PEtOz-CHMC with different MWs and molar ratios was screened by drug release and cytotoxicity experiments at different pH levels. Results indicated that the liposomes coated with PEtOz1k-CHMC (7% molar ratio) and PEtOz2k-CHMC (5% molar ratio) exhibited the desirable pH responsiveness. When the MW of PEtOz was relatively low, 7% of the modified ratio obtained the strongest stability, but the turbidity of the liposomes did not obviously change when the molar ratio of PEtOz-CHMC was further increased. A375 cells were used as models to investigate the cellular uptake and intracellular localization of coumarin-6-loaded liposomes (C6-L), PEGylated liposomes (PEG-C6-L), and PEtOzylated liposomes. PEtOz1k-C6-L and PEtOz2k-C6-L presented remarkably stronger fluorescence intensity at low pH than at pH 7.4, whereas C6-L and PEG-C6-L did not achieve any obvious diversity at different pH conditions. Compared with C6-L and PEG-C6-L, PEtOz-C6-L showed efficient intracellular trafficking, including endosomal/lysosomal escape and cytoplasmic release. Pharmacokinetic experiments demonstrated that half-lives of PEG2k-C6-L, PEtOz2k-C6-L, and PEtOz1k-C6-L were 11.89-, 7.00-, and 5.29-fold times higher than those of C6-L, respectively. Among the liposomes, the DOX·HCl-loaded liposomes coated with PEtOz2k-CHMC demonstrated the strongest antitumor efficacy against B16 tumor xenograft models in vivo. These findings provide the feasibility of using PEtOz-CHMC with optimal pH sensitivity and long circulation to extend the application of liposomes to efficient anticancer drug delivery.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Lipídeos/química , Lipossomos/química , Lipossomos/farmacologia , Poliaminas/química , Animais , Linhagem Celular Tumoral , Cumarínicos/química , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos/efeitos dos fármacos , Endossomos/química , Formiatos/química , Humanos , Concentração de Íons de Hidrogênio , Masculino , Camundongos , Peso Molecular , Polietilenoglicóis/química , Ratos , Ratos Wistar , Tiazóis/química
16.
Mikrochim Acta ; 187(2): 110, 2020 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-31916015

RESUMO

The authors describe a peroxidase-mimicking nanozyme composed of IrO2 and graphene oxide (GO). It was synthesized from monodisperse IrO2 nanoparticles with an average diameter of 1.7 ± 0.3 nm that were prepared by pulsed laser ablation in ethanol. The nanoparticles were then placed on polyallylamine-modified GO nanosheets through electrostatic interaction. The peroxidase-like activity of the resulting nanocomposites was evaluated by catalytic oxidation of 3,3',5,5'-tetramethylbenzidine in the presence of H2O2. Kinetic results demonstrated that the catalytic behavior of the nanocomposites follows Michaelis-Menten kinetics. Experiments performed with terephthalic acid and cytochrome C confirmed that the peroxidase-like activity originated from the electron transfer mechanism rather than from generation of hydroxy radicals. The peroxidase-like activity is inhibited in the presence of ascorbic acid (AA). Based on this property, a colorimetric assay was developed for the determination of AA by exploiting the peroxidase-like activity of IrO2/GO nanocomposites. The linear relationship between absorbance at 652 nm and the concentration of AA was acquired. The limit of detection for AA is 324 nM. Further applications of the method for AA detection in real samples were also successfully demonstrated. Graphical abstractSchematic of the preparation of polyallylamine (PAH)-stabilized IrO2/GO nanocomposites and the colorimetric detection of AA based on the peroxidase-like activity of IrO2/GO nanocomposites.


Assuntos
Ácido Ascórbico/análise , Grafite/química , Irídio/química , Nanopartículas Metálicas/química , Poliaminas/química , Ácido Ascórbico/química , Benzidinas/química , Catálise , Colorimetria/métodos , Corantes/química , Peróxido de Hidrogênio/química , Limite de Detecção , Nanocompostos/química , Oxirredução , Peroxidase/química
17.
Int J Syst Evol Microbiol ; 70(1): 555-561, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31661044

RESUMO

A novel Gram-stain-negative, yellowish-pigmented bacterial strain, designated LA-38T, was isolated from activated sludge of wastewater treatment plants in Hanam city, South Korea. Cell of LA-38T were rod-shaped, aerobic, motile and non-spore-forming. In phylogenetic analyses based on 16S rRNA genes, LA-38T clustered with species of the genus Hydrogenophaga and appeared closely related to Hydrogenophaga intermedia DSM 5680T (99.2 % similarity), Hydrogenophaga palleronii DSM 63T (98.2 %), Hydrogrenophaga laconesensis KCTC 42478T (98.1 %), Hydrogenophaga. atypica DSM 15342T (98.1 %), Hydrogenophaga defluvii DSM 15341T (98.0 %) and Hydrogenophaga taeniospiralis DSM 2082T (97.2 %). The average nucleotide identities between LA-38T and the closely related strains were 79.3-88.5 %, indicating that LA-38T represents a novel species of the genus Hydrogenophaga. The DNA G+C content of the genomic DNA was 69.9 mol% and ubiquinone Q-8 was the predominant respiratory quinone. The major cellular fatty acids (>5 %) were C16 : 0, cyclo-C19 : 0, C16 : 1ω7c and/or C16 : 1ω6c (summed feature 3), and C18 : 1ω7c and/or C18 : 1ω6c (summed feature 8). The major polar lipids consisted of phosphatidylglycerol, diphosphatidylglycerol and phosphatidylethanolamine, the major polyamines were 2-hydroxyputrescine and putrescine. ANI calculation, physiological and biochemical characteristics indicated that LA-38T represents a novel species of the genus Hydrogenophaga, for which the name Hydrogenophaga borbori sp. nov. is proposed. The type strain is LA-38T (=KACC 19730T=LMG 30805T).


Assuntos
Comamonadaceae/classificação , Filogenia , Esgotos/microbiologia , Técnicas de Tipagem Bacteriana , Composição de Bases , Comamonadaceae/isolamento & purificação , DNA Bacteriano/genética , Ácidos Graxos/química , Fosfolipídeos/química , Poliaminas/química , RNA Ribossômico 16S/genética , República da Coreia , Análise de Sequência de DNA , Ubiquinona
18.
Int J Syst Evol Microbiol ; 70(1): 397-405, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31626583

RESUMO

A polyphasic taxonomic approach was used to characterize a nitrogen-fixing bacterium, designated strain CC-HIH110T, isolated from paddy soil in Taiwan. Cells of strain CC-HIH110T were Gram-stain-negative, rod-shaped, motile with polar flagella, catalase-positive and oxidase-positive. Optimal growth occurred at 30 °Ð¡, pH 7 and 1 % NaCl. Phylogenetic analyses based on 16S rRNA genes revealed a distinct taxonomic position attained by strain CC-HIH110T associated with Rhizobium oryziradicis (98.4 % sequence identity), Allorhizobium vitis (97.8 %), Allorhizobium taibaishanense (97.7 %) and Allorhizobium undicola (96.0 %), and lower sequence similarity to other species. Average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between strain CC-HIH110T and the type strains of other closely related species were 71.5-88.6 % and 19.6-35.5 %, respectively. Strain CC-HIH110T contained C16 : 0 3-OH, C14 : 0 3-OH/iso C16 : 1 I and C18 : 1 ω7c/C18  : 1 ω6c as the predominant fatty acids. The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylmonomethylethanolamine, phosphatidyldimethylethanolamine, phosphatidylcholine, three unknown aminophospholipids, two unknown phospholipids and an unknown lipid. The major polyamine was homospermidine. The DNA G+C content was 55.0 mol% and the predominant quinone was ubiquinone (Q-10). Based on its distinct phylogenetic, phenotypic and chemotaxonomic traits together with results of comparative 16S rRNA gene sequence, ANI and dDDH analyses, strain CC-HIH110T is proposed to represent a novel Allorhizobium species, for which the name Allorhizobium terrae sp. nov. (type strain CC-HIH110T=BCRC 80932T=JCM 31228T). In addition, Rhizobium oryziradicis is reclassified as Allorhizobium oryziradicis (type strain N19T=ACCC 19962T=KCTC 52413T) comb. nov.


Assuntos
Oryza , Filogenia , Rhizobiaceae/classificação , Microbiologia do Solo , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Hibridização de Ácido Nucleico , Fosfolipídeos/química , Poliaminas/química , RNA Ribossômico 16S/genética , Rhizobiaceae/isolamento & purificação , Rhizobium , Análise de Sequência de DNA , Taiwan , Ubiquinona/análogos & derivados , Ubiquinona/química
19.
Int J Syst Evol Microbiol ; 70(1): 499-504, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31613737

RESUMO

A novel Gram-stain-negative, aerobic, rod-shaped, reddish-orange-coloured, gliding bacterial strain, designated L12M1T, was isolated from the gut of the Korean scallop, Patinopecten yessoensis. Phylogenetic analysis based on 16S rRNA gene sequence revealed that strain L12M1T formed a monophyletic clade with the strains in the genus Flammeovirga and showed highest 16S rRNA gene sequence similarity to Flammeovirga kamogawensis YS10T (98.66 %). The major cellular fatty acids of strain L12M1T were iso-C15 : 0 and C20 : 4ω6,9,12,15c. The predominant isoprenoid quinone was MK-7. The major polyamines were spermidine, cadaverine and the minor polyamine was putrescine. The DNA G+C content was 32.1 mol%. The phylogenetic, phenotypic, biochemical, chemotaxonomic and genotypic results indicated that strain L12M1T represents a novel species of the genus Flammeovirga, for which the name Flammeovirga pectinis sp. nov. is proposed. The type strain is L12M1T (=KCTC 62750T=JCM 33169T).


Assuntos
Bacteroidetes/classificação , Pectinidae/microbiologia , Filogenia , Animais , Técnicas de Tipagem Bacteriana , Bacteroidetes/isolamento & purificação , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Pigmentação , Poliaminas/química , RNA Ribossômico 16S/genética , República da Coreia , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química
20.
Chemistry ; 26(12): 2749-2753, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-31826315

RESUMO

Poly(2-oxazoline)s (POx) bottle-brush brushes have excellent biocompatible and lubricious properties, which are promising for the functionalization of surfaces for biomedical devices. Herein, a facile synthesis of POx is reported which is based bottle-brush brushes (BBBs) on solid substrates. Initially, backbone brushes of poly(2-isopropenyl-2-oxazoline) (PIPOx) were fabricated via surface initiated Cu0 plate-mediated controlled radical polymerization (SI-Cu0 CRP). Poly(2-methyl-2-oxazoline) (PMeOx) side chains were subsequently grafted from the PIPOx backbone via living cationic ring opening polymerization (LCROP), which result in ≈100 % increase in brush thickness (from 58 to 110 nm). The resultant BBBs shows tunable thickness up to 300 nm and high grafting density (σ) with 0.42 chains nm-2 . The synthetic procedure of POx BBBs can be further simplified by using SI-Cu0 CRP with POx molecular brush as macromonomer (Mn =536 g mol-1 , PDI=1.10), which results in BBBs surface up to 60 nm with well-defined molecular structure. Both procedures are significantly superior to the state-of-art approaches for the synthesis of POx BBBs, which are promising to design bio-functional surfaces.


Assuntos
Materiais Biocompatíveis/síntese química , Oxazóis/síntese química , Cobre/química , Estrutura Molecular , Oxazóis/química , Poliaminas/química , Polimerização , Polipropilenos/química
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