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1.
Int J Nanomedicine ; 16: 1743-1755, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33688189

RESUMO

Background: As a therapeutic target for cancer treatment, HSP90 has been explored extensively. However, the significant side effects of the HSP90 inhibitor 17AAG have limited its clinical use. Methods: In this study, we used hyaluronic acid (HA)-decorated DOTAP-PLGA hybrid nanoparticles (HA-DOTAP-PLGA NPs) as 17AAG-delivery carriers for targeted colon cancer therapy. Results: Different methods were used to characterize the successful fabrication of these hybrid PLGA NPs. Our results demonstrated that internalization of HA-NPs in colon cancer cells was governed by CD44receptor-mediated endocytosis. Annexin V-propidium iodide staining experiments revealed that cell apoptosis induced by HA-NPs-17AAG in colon cancer cells was more efficient than free 17AAG. In two animal models used to screen anticancer efficacy (Luc-HT29 subcutaneous xenograft and AOM/DSS-induced orthotopic tumor model), HA-NPs-17AAG significantly inhibited xenograft and orthotopic tumor growth, demonstrating HA-NPs-17AAG had much better therapeutic efficiency than free 17AAG. It is worth noting that great biocompatibility of HA-DOTAP-PLGA NPs was observed both in vitro and in vivo. Conclusion: Our research offers a preclinical proof of concept for colon cancer therapy with DOTAP-PLGA NPs as a creative drug-delivery system.


Assuntos
Neoplasias do Colo/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Ácido Hialurônico/química , Nanopartículas/química , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Benzoquinonas/farmacologia , Materiais Biocompatíveis/química , Linhagem Celular Tumoral , Neoplasias do Colo/patologia , Endocitose/efeitos dos fármacos , Ácidos Graxos Monoinsaturados/química , Fluorescência , Proteínas de Choque Térmico HSP90/metabolismo , Humanos , Receptores de Hialuronatos/metabolismo , Lactamas Macrocíclicas/farmacologia , Camundongos , Nanopartículas/administração & dosagem , Nanopartículas/ultraestrutura , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Compostos de Amônio Quaternário/química , Tela Subcutânea/efeitos dos fármacos , Tela Subcutânea/patologia
2.
Methods Mol Biol ; 2246: 87-96, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33576984

RESUMO

Oligonucleotides able to hybridize bacterial RNA via in situ hybridization may potentially act as new antimicrobials, replacing antibiotics, and as fast in vivo diagnostic probes, outperforming current clinical methodologies. Nonetheless, oligonucleotides are not able to efficiently permeate the multi-layered bacterial envelope to reach their target RNA in the cytosol. Cationic fusogenic liposomes are here suggested as vehicles to enable the internalization of oligonucleotides in bacteria. Here, we describe the formulation of DOTAP-DOPE liposomes, their complexation with small negatively charged oligonucleotides, and the evaluation of the intracellular delivery of the oligonucleotides in bacteria. This strategy uncovers the potential of performing FISH in vivo for real-time detection and treatment of infections.


Assuntos
Bactérias/metabolismo , Lipossomos/química , Oligonucleotídeos/metabolismo , Cátions/química , Citosol/metabolismo , Ácidos Graxos Monoinsaturados/química , Hibridização in Situ Fluorescente/métodos , Fosfatidiletanolaminas/química , Compostos de Amônio Quaternário/química , RNA Bacteriano/metabolismo
3.
Sci Rep ; 11(1): 2418, 2021 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-33510320

RESUMO

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is currently a global pandemic, and there are limited laboratory studies targeting pathogen resistance. This study aimed to investigate the effect of selected disinfection products and methods on the inactivation of SARS-CoV-2 in the laboratory. We used quantitative suspension testing to evaluate the effectiveness of the disinfectant/method. Available chlorine of 250 mg/L, 500 mg/L, and 1000 mg/L required 20 min, 5 min, and 0.5 min to inactivate SARS-CoV-2, respectively. A 600-fold dilution of 17% concentration of di-N-decyl dimethyl ammonium bromide (283 mg/L) and the same concentration of di-N-decyl dimethyl ammonium chloride required only 0.5 min to inactivate the virus efficiently. At 30% concentration for 1 min and 40% and above for 0.5 min, ethanol could efficiently inactivate SARS-CoV-2. Heat takes approximately 30 min at 56 °C, 10 min above 70 °C, or 5 min above 90 °C to inactivate the virus. The chlorinated disinfectants, Di-N-decyl dimethyl ammonium bromide/chloride, ethanol, and heat could effectively inactivate SARS-CoV-2 in the laboratory test. The response of SARS-CoV-2 to disinfectants is very similar to that of SARS-CoV.


Assuntos
Desinfetantes/farmacologia , Desinfecção/métodos , Inativação de Vírus/efeitos dos fármacos , /prevenção & controle , Cloro/química , Cloro/farmacologia , Desinfetantes/química , Etanol/química , Etanol/farmacologia , Humanos , Pandemias/prevenção & controle , Compostos de Amônio Quaternário/química , Compostos de Amônio Quaternário/farmacologia
4.
Phys Chem Chem Phys ; 23(2): 944-959, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33367394

RESUMO

The nanostructure in water solutions of three organic ionic liquids relevant for biological applications has been studied by molecular dynamics simulations based on empirical force fields. The three compounds consisted of two different triethylammonium salts, known to affect the fibrillation kinetics of Aß peptides, and a phosphonium dication, which has been shown to possess a marked bactericidal activity. The structure of solutions spanning a wide concentration range (from 25 to 75 wt%) has been analysed by computing several combinations of partial structure factors, measuring the fluctuation of the ion and water distribution in space. At moderate salt concentration, the results reflect the formation in water of salt-rich domains of nanometric size. With salt concentration increasing beyond 50 wt%, the system enters the so-called water-in-salt regime, in which the aggregation properties of water become relevant, giving origin to water-rich domains in the nearly uniform salt environment. The persistence over a wide concentration range of nearly integer (∼6; ∼4) water-ion coordination numbers suggests the formation of stoichiometric liquid ionic hydrates.


Assuntos
Líquidos Iônicos/química , Nanoestruturas/química , Água/química , Condutividade Elétrica , Ligação de Hidrogênio , Simulação de Dinâmica Molecular , Transição de Fase , Compostos de Amônio Quaternário/química , Termodinâmica
5.
Food Chem ; 334: 127559, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32711270

RESUMO

This study approaches the development of a method for the determination of Ca, Mg, Zn, and Fe in liquid and powdered cow milk. The method is based on sample dissolution assisted by ultrasound energy in tetramethylammonium hydroxide (TMAH) media and determination by flame atomic absorption spectrometry (FAAS). Central composite design (CCD) associated with response surface methodology and desirability function allowed the fast and efficient optimization of the variables involved in the performance of the dissolution. The developed dissolution method allowed Ca, Fe, Zn, and Mg determination in milk samples with adequate analytical characteristics for these determinations. Addition/recovery tests and analysis of a certified reference material of skimmed powdered milk (ERM-BD150) have shown that this method presents enough accuracy to carry out these analyses.


Assuntos
Análise de Alimentos/métodos , Metais/análise , Leite/química , Compostos de Amônio Quaternário/química , Espectrofotometria Atômica/métodos , Animais , Bovinos , Feminino , Análise de Alimentos/estatística & dados numéricos , Análise Multivariada , Pós , Solubilidade
6.
Int J Mol Sci ; 21(24)2020 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-33327408

RESUMO

The tear film at the ocular surface is covered by a thin layer of lipids. This oily phase stabilizes the film by decreasing its surface tension and improving its viscoelastic properties. Clinically, destabilization and rupture of the tear film are related to dry eye disease and are accompanied by changes in the quality and quantity of tear film lipids. In dry eye, eye drops containing oil-in-water emulsions are used for the supplementation of lipids and surface-active components to the tear film. We explore in detail the biophysical aspects of interactions of specific surface-active compounds, cetalkonium chloride and poloxamer 188, which are present in oil-in-water emulsions, with tear lipids. The aim is to better understand the macroscopically observed eye drops-tear film interactions by rationalizing them at the molecular level. To this end, we employ a multi-scale approach combining experiments on human meibomian lipid extracts, measurements using synthetic lipid films, and in silico molecular dynamics simulations. By combining these methods, we demonstrate that the studied compounds specifically interact with the tear lipid film enhancing its structure, surfactant properties, and elasticity. The observed effects are cooperative and can be further modulated by material packing at the tear-air interface.


Assuntos
Lipídeos/química , Microscopia de Fluorescência/métodos , Simulação de Dinâmica Molecular , Filmes Cinematográficos , Álcoois Graxos/química , Humanos , Glândulas Tarsais/metabolismo , Modelos Teóricos , Poloxâmero/química , Compostos de Amônio Quaternário/química
8.
Cells ; 9(9)2020 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-32899484

RESUMO

Hybrid nanoparticles from lipidic and polymeric components were assembled to serve as vehicles for the transfection of messenger RNA (mRNA) using different portions of the cationic lipid DOTAP (1,2-Dioleoyl-3-trimethylammonium-propane) and the cationic biopolymer protamine as model systems. Two different sequential assembly approaches in comparison with a direct single-step protocol were applied, and molecular organization in correlation with biological activity of the resulting nanoparticle systems was investigated. Differences in the structure of the nanoparticles were revealed by thorough physicochemical characterization including small angle neutron scattering (SANS), small angle X-ray scattering (SAXS), and cryogenic transmission electron microscopy (cryo-TEM). All hybrid systems, combining lipid and polymer, displayed significantly increased transfection in comparison to lipid/mRNA and polymer/mRNA particles alone. For the hybrid nanoparticles, characteristic differences regarding the internal organization, release characteristics, and activity were determined depending on the assembly route. The systems with the highest transfection efficacy were characterized by a heterogenous internal organization, accompanied by facilitated release. Such a system could be best obtained by the single step protocol, starting with a lipid and polymer mixture for nanoparticle formation.


Assuntos
Biopolímeros/química , Lipídeos/química , Nanopartículas/química , RNA Mensageiro/metabolismo , Transfecção/métodos , Animais , Linhagem Celular , Ácidos Graxos Monoinsaturados/química , Feminino , Heparina/química , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Imagem Óptica , Tamanho da Partícula , Compostos de Amônio Quaternário/química , RNA Mensageiro/química
9.
J Oleo Sci ; 69(9): 1021-1030, 2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32788513

RESUMO

A novel jellyfish-shaped triazine hexamer quaternary ammonium chloride surfactant (TH12QC) was synthesized, which consisted of one triazine spacer group and six long flexible hydrophobic chains. The molecular structure and aggregation behavior of TH12QC was investigated by nuclear magnetic resonance (NMR), surface tension, electrical conductivity, dynamic light scattering (DLS), transmission electron microscope (TEM), etc. The results show that the jellyfish-shaped TH12QC has better surface activity and lower surface tension than traditional ionic and Gemini surfactants in aqueous solution. There are two inflection points in the curve of conductivity versus concentration of the TH12QC aqueous solution, which correspond to the critical aggregation concentration (CAC) and the critical micelle concentration (CMC) respectively. The existence of CAC indicates that there is a pre-aggregation process before TH12QC forms micelles. The results of DLS and TEM show that network pre-aggregation, spherical aggregation and dense spherical aggregation were observed in different concentration of TH12QC aqueous solution, and the electrostatic equilibrium of the system subtly depends on the concentration of the solution. In addition, intramolecular and intermolecular hydrogen bonding is also an important factor. This study provides a method for studying the aggregation behavior and morphology of oligomeric surfactants with rigid spacer groups.


Assuntos
Cloreto de Amônio/química , Cloreto de Amônio/síntese química , Compostos de Amônio Quaternário/química , Compostos de Amônio Quaternário/síntese química , Tensoativos/química , Tensoativos/síntese química , Triazinas/química , Triazinas/síntese química , Fenômenos Químicos , Difusão Dinâmica da Luz , Condutividade Elétrica , Ligação de Hidrogênio , Micelas , Estrutura Molecular , Soluções , Tensão Superficial , Água/química
10.
Chemosphere ; 260: 127681, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32758785

RESUMO

In this work, magnetic separably barium ferrite nanomaterial (BaFeO) was synthesized via citrate acid assisted sol-gel combustion method. Subsequently, X-ray diffraction (XRD), scanning electron microscopy-energy dispersion spectroscopy (SEM-EDS), transmission electron microscopy (TEM) and vibrating sample magnetometer (VSM) were applied for its structural, morphological, and electromagnetic characterization. In addition, microwave (MW) absorption and thermal conversion test results indicated the BaFeO had electrothermal rather than magnetothermal conversion capacity. Meanwhile, the synthesized BaFeO showed satisfactory performance in both eliminating and mineralization of a typical triphenylmethane dye, brilliant green (BG), in MW-induced catalytic oxidation (MICO) process without extra oxidant addition. Besides, changes in element valence and content of BaFeO before and after MICO process investigated with XRD, Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) showed its relatively stable properties. Furthermore, transition oxygen species involved in MICO process was deduced as lattice oxygen species. Then, the possible degradation pathway of BG was proposed as demethylation, open-loop of triphenylmethane, releasing one ring, formation of the benzene ring and the ultimate mineralization based on the degradation intermediates tentatively identified by gas chromatography mass spectrometry (GC/MS) and liquid chromatography mass spectrometry (LC/MS), respectively. Finally, ecotoxicity analysis by ecological structure activity relationships (ECOSAR) showed that both the acute and chronic toxicity of these intermediates were lower than that of parent BG. These findings are important regarding the development of efficient catalysts in MICO process for degradation of BG analogues in wastewater.


Assuntos
Compostos de Bário/química , Compostos Férricos/química , Nanoestruturas/química , Compostos de Amônio Quaternário/química , Catálise , Corantes/química , Magnetismo , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Micro-Ondas , Espectroscopia Fotoeletrônica , Águas Residuárias , Difração de Raios X
11.
Int J Nanomedicine ; 15: 5873-5899, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32848395

RESUMO

Supramolecular vesicles are the most popular smart nano-drug delivery systems (SDDs) because of their unique cavities, which have high loading carrying capacity and controlled-release action in response to specific stimuli. These vesicles are constructed from amphiphilic molecules via host-guest complexation, typically with targeted stimuli-responsive units, which are particularly important in biotechnology and biomedicine applications. Amphiphilic pillar[n]arenes, which are novel and functional macrocyclic host molecules, have been widely used to construct supramolecular vesicles because of their intrinsic rigid and symmetrical structure, electron-rich cavities and excellent properties. In this review, we first explain the synthesis of three types of amphiphilic pillar[n]arenes: neutral, anionic and cationic pillar[n]arenes. Second, we examine supramolecular vesicles composed of amphiphilic pillar[n]arenes recently used for the construction of SDDs. In addition, we describe the prospects for multifunctional amphiphilic pillar[n]arenes, particularly their potential in novel applications.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Nanoestruturas/química , Compostos de Amônio Quaternário/química , Animais , Cátions/química , Humanos , Compostos de Amônio Quaternário/síntese química
12.
J Chromatogr A ; 1625: 461282, 2020 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-32709333

RESUMO

In recent years, core-shell silica particles (CSSPs) have been increasingly used for highly efficient separation at fast flow rates and relatively low back pressures in high-performance liquid chromatography (HPLC). However, material synthesis techniques for producing CSSPs economically in batch processes remain elusive. In this report, a practical and straightforward method for the preparation of CSSPs is presented. By refluxing freshly prepared nonporous silica particles in ammonia-water solution in the presence of poly(diallyldimethylammonium chloride) at 70-100 °C, CSSPs with shell thicknesses of up to 300 nm and pore sizes from 8 to 25 nm were easily prepared. The effects of the synthetic conditions on the shell thickness, surface area, and pore size were investigated in detail, and the method reproducibility was evaluated in scale-up experiments. A mechanism of CSSP formation is also proposed. The CSSPs were characterized via scanning electron microscopy, transmission electron microscopy, laser particle size (dynamic light scattering) analysis, and nitrogen adsorption and desorption experiments. The synthesized 3.4-µm CSSPs were functionalized with dimethyloctadecylchlorosilane and used as an HPLC packing material, exhibiting excellent separation performance for both small molecules and large biomolecules. In summary, we report the simplest method developed thus far for the preparation of monodisperse core-shell silica particles suitable for HPLC column packing.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Sílica Gel/química , Adsorção , Amônia/análise , Difusão Dinâmica da Luz , Microesferas , Peso Molecular , Nanopartículas/química , Nanopartículas/ultraestrutura , Tamanho da Partícula , Polietilenos/química , Porosidade , Compostos de Amônio Quaternário/química , Reprodutibilidade dos Testes , Temperatura , Fatores de Tempo
13.
J Oleo Sci ; 69(6): 549-555, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32522916

RESUMO

Foam separation can selectively remove a target substance from a solution via adsorption of the substance with the surfactant at the surface of the bubble. A cationic dye, methylene blue, and an anionic dye, Fast Green FCF, were prepared as substances to be removed via foam separation. Anionic (sodium dodecyl sulfate, SDS), cationic (dodecyltrimethylammonium chloride, DTAC), and amphoteric (3-(dodecyldimethylammonio)propane-1-sulfonate, SB-12) surfactants were used in the foam separation process. The effectiveness of the surfactants for removing the cationic methylene blue increased as follows: DTAC < SB-12 < SDS. On the other hand, the effectiveness of the surfactants for removing the anionic Fast Green FCF was in the opposite order. The dyes were effectively adsorbed by the foams via electrostatic interactions between the oppositely charged surfactant and the dye molecules. Since amphoteric surfactants have both anionic and cationic charges in a molecule, they could effectively remove both dyes in the foam separation process. Therefore, it was found that the amphoteric surfactant was highly versatile. Analysis of the kinetics of the removal rate showed that the aqueous solutions of monomers could remove the dyes more effectively than micellar solutions in foam separation.


Assuntos
Corantes/química , Corantes Verde de Lissamina/química , Azul de Metileno/química , Compostos de Amônio Quaternário/química , Dodecilsulfato de Sódio/química , Tensoativos/química , Adsorção , Sistemas de Transporte de Aminoácidos Básicos , Ânions , Eletricidade Estática
14.
J Oleo Sci ; 69(6): 563-567, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32522917

RESUMO

Foam separation promotes the removal of dissolved materials from solutions by adsorbing the molecules onto a surfactant. The zwitterion of rhodamine B was removed by using both anionic (sodium dodecyl sulfate: SDS) and cationic (dodecyltrimethylammonium chloride: DTAC) surfactants through foam separation. However, rhodamine B could not be removed from a strongly acidic DTAC solution (pH 2), because the molecular form changes from the zwitterion to cation. Moreover, the cationic dye of rhodamine 6G could not be removed from the DTAC solution. Therefore, these results demonstrate that the electrostatic interaction between a surfactant and target ion is an important factor in foam separation.


Assuntos
Compostos de Amônio Quaternário/química , Rodaminas/isolamento & purificação , Dodecilsulfato de Sódio/química , Tensoativos/química , Adsorção , Cátions , Concentração de Íons de Hidrogênio , Íons , Soluções , Eletricidade Estática
15.
J Oleo Sci ; 69(7): 703-710, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32522945

RESUMO

A series of gemini quaternary ammonium surfactants containing carboxylate counterion with the formula C17H35CONH(CH2)2N+(CH3)2(CH2)2N+(CH3)2(CH2)2 NHCO C17H35·2Y (Y=HCOO-, CH3COO-, CH3CHOHCOO-) have been synthesized by a counterion conversion process and characterized by Fourier transform infrared spectroscopy and mass spectroscopy. It is found that these surfactants reduce the surface tension of water to a minimum value of 26.78 mN·m-1 at a concentration of 1.21 ×10-5 mol·L-1. TEM images reveal that aggregates with vesicles or tubular structure are spontaneously formed in these surfactants aqueous solution with the concentration of 1×10-3 mol·L-1. It is also found that they are effective corrosion inhibitors for A3 steel in acid solution and have superior antibacterial activity at a concentration of 0.1g·L-1.


Assuntos
Antibacterianos , Corrosão , Compostos de Amônio Quaternário/química , Compostos de Amônio Quaternário/farmacologia , Aço , Propriedades de Superfície , Tensoativos/química , Relação Dose-Resposta a Droga , Microscopia Eletrônica de Transmissão , Conformação Molecular , Imagem Molecular , Psicoterapia Breve , Compostos de Amônio Quaternário/síntese química , Tensoativos/síntese química , Água
16.
Nanotoxicology ; 14(7): 869-892, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32536294

RESUMO

Surface modification by different quaternary ammonium compounds (QAC) makes nanoclays more compatible with various polymeric matrices, thereby expanding their potential applications. The growing industrial use of nanoclays could potentially pose a health risk for workers. Here, we assessed how surface modification of nanoclays modulates their pulmonary toxicity. An in vitro screening of the unmodified nanoclay Bentonite (montmorillonite) and four organomodified nanoclays (ONC); coated with various QAC, including benzalkonium chloride (BAC), guided the selection of the materials for the in vivo study. Mice were exposed via a single intratracheal instillation to 18, 54, and 162 µg of unmodified Bentonite or dialkyldimethyl-ammonium-coated ONC (NanofilSE3000), or to 6, 18, and 54 µg of a BAC-coated ONC (Nanofil9), and followed for one, 3, or 28 days. All materials induced dose- and time-dependent responses in the exposed mice. However, all doses of Bentonite induced larger, but reversible, inflammation (BAL neutrophils) and acute phase response (Saa3 gene expression in lung) than the two ONC. Similarly, highest levels of DNA strand breaks were found in BAL cells of mice exposed to Bentonite 1 day post-exposure. A significant increase of DNA strand breaks was detected also for NanofilSE3000, 3 days post-exposure. Only mice exposed to Bentonite showed increased Tgf-ß gene expression in lung, biomarker of pro-fibrotic processes and hepatic extravasation, 3 days post-exposure. This study indicates that Bentonite treatment with some QAC changes main physical-chemical properties, including shape and surface area, and may decrease their pulmonary toxicity in exposed mice.


Assuntos
Reação de Fase Aguda/prevenção & controle , Bentonita/toxicidade , Dano ao DNA , Pulmão/efeitos dos fármacos , Nanopartículas/toxicidade , Compostos de Amônio Quaternário/química , Reação de Fase Aguda/imunologia , Animais , Bentonita/química , Líquido da Lavagem Broncoalveolar/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/imunologia , Feminino , Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação , Pulmão/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Nanopartículas/química , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Tamanho da Partícula , Propriedades de Superfície
17.
Cell Immunol ; 354: 104143, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32563850

RESUMO

Immunization with synthetic mRNA encoding tumor-associated antigens is an emerging vaccine strategy for the treatment of cancer. In order to prevent mRNA degradation, promote antigen-presenting cells antigen presentation, and induce an anti-tumor immune response, we investigated the nasal administration of mRNA vaccines with positively charged protamine to concentrate mRNA, form a stable polycation-mRNA complex, and encapsulate the complex with DOTAP/Chol/DSPE-PEG cationic liposomes. Cationic liposome/protamine complex (LPC) showed significantly greater efficiency in uptake of vaccine particles in vitro and stronger capacities to stimulate dendritic cell maturation, which further induced a potent anti-tumor immune response. Intranasal immunization of mice with cationic LPC containing mRNA encoding cytokeratin 19 provoked a strong cellular immune response and slowed tumor growth in an aggressive Lewis lung cancer model. The results of this study provide evidence that cationic LPC can be used as a safe and effective adjuvant and this mRNA formulation provides a basis for anti-cancer vaccination of humans.


Assuntos
Vacinas Anticâncer/imunologia , Células Dendríticas/imunologia , Imunoterapia/métodos , Queratina-19/genética , Lipossomos/imunologia , Neoplasias Pulmonares/terapia , RNA Mensageiro/imunologia , Administração Intranasal , Animais , Carcinoma Pulmonar de Lewis , Diferenciação Celular , Ácidos Graxos Monoinsaturados/química , Feminino , Humanos , Lipossomos/química , Neoplasias Pulmonares/imunologia , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos C57BL , Transplante de Neoplasias , Protaminas/química , Compostos de Amônio Quaternário/química , RNA Mensageiro/química , RNA Mensageiro/genética , Carga Tumoral
18.
Chemosphere ; 258: 127146, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32531298

RESUMO

Tetramethylammonium hydroxide (TMAH) was often used as developer in the high-tech industries. Information regarding biological treatment of high TMAH-containing wastewater is limited. This study investigated aerobic degradation of high TMAH, its impacts on nitrification, and microbial community in a sequencing batch reactor (SBR). The initial TMAH concentrations of SBR gradually increased from 200 to 4666 mg L-1 (equivalent to 31 to 718 mg-N L-1) to enrich microbial community for aerobic TMAH degradation and nitrification. The results indicated that the aerobic specific TMAH degradation rates followed the Monod-type kinetics with a maximum specific TMAH degradation rate of 2.184 mg N hour-1 g volatile suspended solid (VSS)-1 and the half-saturation coefficient of 175.1 mg N L-1. After TMAH degradation and ammonia release, the lag time for the onset of nitrification highly correlated with initial TMAH fed for the SBR. According to the microbial community analysis using next generation sequencing (NGS), potential aerobic TMAH-degraders including Mycobacterium sp. and Hypomicrobium sp. were enriched in the aerobic SBR. The results of real-time quantitative polymerase chain reaction (qPCR) and reverse transcript (RT)-qPCR indicated that Hyphomicrobium sp. may be able to utilize both TMAH and its degradation intermediates such as trimethylamine (TMA), while Thiobacillus sp. can only utilize TMAH. The qPCR and RT-qPCR results suggested that TMAH may inhibit nitrification by inactive expression of amoA gene and the intermediates of TMAH degradation may compete ammonia monooxygenase (AMO) enzyme with ammonia for nitrification inhibition.


Assuntos
Microbiota/fisiologia , Compostos de Amônio Quaternário/metabolismo , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/metabolismo , Aerobiose , Amônia/metabolismo , Biodegradação Ambiental , Reatores Biológicos/microbiologia , Sequenciamento de Nucleotídeos em Larga Escala , Microbiota/genética , Mycobacterium/genética , Mycobacterium/metabolismo , Nitrificação , Compostos de Amônio Quaternário/química , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Thiobacillus/metabolismo , Eliminação de Resíduos Líquidos/instrumentação , Águas Residuárias/química , Poluentes Químicos da Água/química
19.
J Chromatogr A ; 1623: 461130, 2020 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-32505268

RESUMO

The interactions and dynamic behavior of a select set of polar probe solutes have been investigated on three hydrophilic and polar commercial stationary phases using saturation transfer difference 1H nuclear magnetic resonance (STD-NMR) spectroscopy under magic angle spinning conditions. The stationary phases were equilibrated with a select set of polar solutes expected to show different interaction patterns in mixtures of deuterated acetonitrile and deuterium oxide, with ammonium acetate added to a total concentration that mimics typical eluent conditions for hydrophilic interaction chromatography (HILIC). The methylene groups of the stationary phases were selectively irradiated to saturate the ligand protons, at frequencies that minimized the overlaps with reporting protons in the test probes. During and after this radiation, the saturation rapidly spreads to all protons in the stationary phase by spin diffusion, and from those to probe protons in contact with the stationary phase. Probe protons that have been in close contact with the stationary phase and subsequently been released to the solution phase will have been more saturated due to a more efficient transfer of spin polarization by the nuclear Overhauser effect. They will therefore show a higher signal after processing of the data. Saturation transfers to protons in neutral and charged solutes could in some instances show clear orientation patterns of these solutes towards the stationary phases. The saturation profile of formamide and its N-methylated counterparts showed patterns that could be interpreted as oriented hydrogen bond interaction. From these studies, it is evident that the functional groups on the phase surface have a strong contribution to the selectivity in HILIC, and that the retention mechanism has a significant contribution from oriented interactions.


Assuntos
Interações Hidrofóbicas e Hidrofílicas , Espectroscopia de Ressonância Magnética/métodos , Ácido Benzoico/química , Dimetilformamida/química , Concentração de Íons de Hidrogênio , Compostos de Amônio Quaternário/química , Eletricidade Estática
20.
Eur J Med Chem ; 200: 112403, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32447198

RESUMO

By linking two N-methyl-N-carbocyclic quaternary ammonium groups to an azobenzene scaffold in meta- or para-positions we generated a series of photoswitchable neuromuscular ligands for which we coined the term "azocuroniums". These compounds switched between the (E)- and (Z)-isomers by light irradiation at 400-450 nm and 335-340 nm, respectively. Meta-azocuroniums were potent nicotinic ligands with a clear selectivity for the muscular nAChRs compared to neuronal α7 and α4ß2 subtypes, showed good solubility in physiologic media, negligible cell toxicity, and would not reach the CNS. Electrophysiological studies in muscle-type nAChRs expressed in Xenopus laevis oocytes showed that (E)-isomers were more potent than (Z)-forms. All meta-azocuroniums were neuromuscular blockers, with the exception of the pyrrolidine derivative that was an agonist. These new meta-azocuroniums, which can be modulated ad libitum by light, could be employed as photoswitchable muscle relaxants with fewer side effects for surgical interventions and as tools to better understand the pharmacology of muscle-type nAChRs.


Assuntos
Fármacos Neuromusculares/efeitos da radiação , Agonistas Nicotínicos/química , Receptores Nicotínicos/metabolismo , Animais , Compostos Azo/química , Humanos , Isomerismo , Ligantes , Luz , Fármacos Neuromusculares/síntese química , Agonistas Nicotínicos/efeitos da radiação , Oócitos , Compostos de Amônio Quaternário/química , Relação Estrutura-Atividade , Xenopus laevis
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