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1.
Inhal Toxicol ; 33(9-14): 334-346, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34890527

RESUMO

OBJECTIVE: Ethyltoluenes are isolated during crude oil refinement for use in gasoline and commercial products and are ubiquitous in the environment. However, minimal toxicity data are available. Previously, we identified 2-ethyltoluene (2-ET) as the most potent isomer via nose-only inhalation exposure in rodents. Here, we expanded the hazard characterization of 2-ET in two rodent models using whole-body inhalation exposure and evaluated the role of prenatal exposure. METHODS: Time-mated Hsd:Sprague Dawley® SD® rats were exposed to 0, 150, 300, 600, 900, or 1200 ppm 2-ET via inhalation starting on gestation day 6 until parturition. Rat offspring (n = 8/exposure/sex) were exposed to the same concentrations as the respective dams for 2 weeks after weaning. Adult male and female B6C3F1/N mice (n = 5/exposure/sex) were exposed to the same concentrations for 2 weeks. RESULTS AND DISCUSSION: Exposure to ≥600 ppm 2-ET produced acute toxicity in rats and mice characterized by large decreases in survival, body weight, adverse clinical observations, and diffuse nasal olfactory epithelium degeneration (rats) or necrosis (mice). Due to the early removal of groups ≥600 ppm, most endpoint evaluations focused on lower exposure groups. In 150 and 300 ppm exposure groups, reproductive performance and littering were not significantly changed and body weights in exposed rats and mice were 9-18% lower than controls. Atrophy of the olfactory epithelium and nerves was observed in all animals exposed to 150 and 300 ppm. These lesions were more severe in mice than in rats. CONCLUSION: Nasal lesions were observed in all animals after whole-body exposure up to 600 ppm 2-ET for 2 weeks. Future studies should focus on 2-ET metabolism and distribution to better understand species differences and refine hazard characterization of this understudied environmental contaminant.


Assuntos
Exposição por Inalação , Administração por Inalação , Animais , Feminino , Exposição por Inalação/efeitos adversos , Masculino , Camundongos , Camundongos Endogâmicos , Gravidez , Ratos , Ratos Endogâmicos F344 , Ratos Sprague-Dawley
2.
Inhal Toxicol ; 31(5): 192-202, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31345048

RESUMO

Background: Increasing evidence from rodent studies indicates that inhaled multi-walled carbon nanotubes (MWCNTs) have harmful effects on the lungs. In this study, we examined the effects of inhalation exposure to MWCNTs on allergen-induced airway inflammation and fibrosis. We hypothesized that inhalation pre-exposure to MWCNTs would render mice susceptible to developing allergic lung disease induced by house dust mite (HDM) allergen. Methods: Male B6C3F1/N mice were exposed by whole-body inhalation for 6 h a day, 5 d a week, for 30 d to air control or 0.06, 0.2, and 0.6 mg/m3 of MWCNTs. The exposure atmospheres were agglomerates (1.4-1.8 µm) composed of MWCNTs (average diameter 16 nm; average length 2.4 µm; 0.52% Ni). Mice then received 25 µg of HDM extract by intranasal instillation 6 times over 3 weeks. Necropsy was performed at 3 and 30 d after the final HDM dose to collect serum, bronchoalveolar lavage fluid (BALF), and lung tissue for histopathology. Results: MWCNT exposure at the highest dose inhibited HDM-induced serum IgE levels, IL-13 protein levels in BALF, and airway mucus production. However, perivascular and peribronchiolar inflammatory lesions were observed in the lungs of mice at 3 d with MWCNT and HDM, but not MWCNT or HDM alone. Moreover, combined HDM and MWCNT exposure increased airway fibrosis in the lungs of mice. Conclusions: Inhalation pre-exposure to MWCNTs inhibited HDM-induced TH2 immune responses, yet this combined exposure resulted in vascular inflammation and airway fibrosis, indicating that MWCNT pre-exposure alters the immune response to allergens.


Assuntos
Antígenos de Dermatophagoides/imunologia , Hipersensibilidade/fisiopatologia , Exposição por Inalação/efeitos adversos , Pulmão/fisiologia , Nanotubos de Carbono/toxicidade , Animais , Líquido da Lavagem Broncoalveolar , Relação Dose-Resposta Imunológica , Fibrose , Imunoglobulina E/sangue , Interleucina-13/análise , Masculino , Camundongos , Células Th2/imunologia
3.
Inhal Toxicol ; 29(9): 414-427, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-29039228

RESUMO

ortho-Phthalaldehyde (OPA) is a high-level chemical disinfectant that is commonly used for chemical sterilization of dental and medical instruments as an alternative to glutaraldehyde, a known skin and respiratory sensitizer. Concern for safe levels of human exposure remains due to a lack of toxicity data as well as human case reports of skin and respiratory sensitization following OPA exposure. The present study evaluated the inhalational toxicity of OPA in Harlan Sprague-Dawley rats and B6C3F1/N mice. Groups of 10 male and female rats and mice were exposed to OPA by whole-body inhalation for 3 months at concentrations of 0 (control), 0.44, 0.88, 1.75, 3.5, or 7.0 ppm. Rats and mice developed a spectrum of lesions at sites of contact throughout the respiratory tract (nose, larynx, trachea, lung), as well as in the skin and eye, consistent with a severe irritant response. In general, histologic lesions (necrosis, inflammation, regeneration, hyperplasia and metaplasia) occurred at deeper sites within the respiratory tract with increasing exposure concentration. As a first site of contact, the nose exhibited the greatest response to OPA exposure and resulted in an increased incidence, severity and variety of lesions compared to a previous study of glutaraldehyde exposure at similar exposure concentrations. This increased response in the nasal cavity, combined with extensive lesions throughout the respiratory tract, provides concern for use of OPA as a replacement for glutaraldehyde as a high-level disinfectant.


Assuntos
Desinfetantes/toxicidade , Glutaral/toxicidade , Sistema Respiratório/efeitos dos fármacos , o-Ftalaldeído/toxicidade , Administração por Inalação , Animais , Feminino , Masculino , Camundongos , Ratos Sprague-Dawley , Sistema Respiratório/patologia
4.
Nanotoxicology ; 10(10): 1458-1468, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27618498

RESUMO

C60 fullerene (C60), or buckminsterfullerene, is a spherical arrangement of 60 carbon atoms, having a diameter of approximately 1 nm, and is produced naturally as a by-product of combustion. Due to its small size, C60 has attracted much attention for use in a variety of applications; however, insufficient information is available regarding its toxicological effects. The effects on respiratory toxicity and immunotoxicity of C60 aggregates (50 nm [nano-C60] and 1 µm [micro-C60] diameter) were examined in B6C3F1/N mice and Wistar Han rats after nose-only inhalation for 13 weeks. Exposure concentrations were selected to allow for data evaluations using both mass-based and particle surface area-based exposure metrics. Nano-C60 exposure levels selected were 0.5 and 2 mg/m3 (0.033 and 0.112 m2/m3), while micro-C60 exposures were 2, 15 and 30 mg/m3 (0.011, 0.084 and 0.167 m2/m3). There were no systemic effects on innate, cell-mediated, or humoral immune function. Pulmonary inflammatory responses (histiocytic infiltration, macrophage pigmentation, chronic inflammation) were concentration-dependent and corresponded to increases in monocyte chemoattractant protein (MCP)-1 (rats) and macrophage inflammatory protein (MIP)-1α (mice) in bronchoalveolar lavage (BAL) fluid. Lung overload may have contributed to the pulmonary inflammatory responses observed following nano-C60 exposure at 2 mg/m3 and micro-C60 exposure at 30 mg/m3. Phenotype shifts in cells recovered from the BAL were also observed in all C60-exposed rats, regardless of the level of exposure. Overall, more severe pulmonary effects were observed for nano-C60 than for micro-C60 for mass-based exposure comparisons. However, for surface-area-based exposures, more severe pulmonary effects were observed for micro-C60 than for nano-C60, highlighting the importance of dosimetry when evaluating toxicity between nano- and microparticles.


Assuntos
Fulerenos/toxicidade , Exposição por Inalação/efeitos adversos , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Nanopartículas/toxicidade , Pneumonia/induzido quimicamente , Animais , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/imunologia , Relação Dose-Resposta a Droga , Fulerenos/química , Imunidade Celular/efeitos dos fármacos , Imunidade Humoral/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Exposição por Inalação/análise , Masculino , Camundongos , Nanopartículas/química , Tamanho da Partícula , Pneumonia/imunologia , Ratos , Ratos Wistar , Propriedades de Superfície
5.
Toxicology ; 339: 87-96, 2016 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-26612504

RESUMO

C60 fullerenes (C60) are spherical structures consisting of 60 carbon atoms that are generated via combustion from both natural and anthropogenic sources. C60 are also synthesized intentionally for industrial applications. Individual C60 structures have an approximate diameter of 1nm; however, C60 readily forms aggregates and typically exist as larger particles that range from nanometers to micrometers in diameter. In this report, lung and extrapulmonary tissue deposition and lung clearance of C60 nanoparticles (nano-C60, 50nm) and microparticles (micro-C60, 1µm) were examined in Wistar Han rats and B6C3F1/N mice after nose-only inhalation for 90 days. Exposure concentrations were 0.5 and 2mg/m(3) (nano-C60) and 2, 15, and 30mg/m(3) (micro-C60). For both C60 particle sizes, the C60 lung burden increased proportionally to exposure concentration. The C60 lung burden was greater in both species at all time points following exposure to nano-C60 particle exposure compared to micro-C60 exposure at the common exposure concentration 2mg/m(3). The calculated C60 particle lung retention half-times were similar for both nano-C60 and micro-C60 exposure at 2mg/m(3) in male mice (15-16 days). In contrast, in male rats, the half-time of C60 particles following nano-C60 exposure (61 days) was roughly twice as long as the half-time following micro-C60 exposure (27 days) at the same exposure concentration (2mg/m(3)) and was similar to the clearance following micro-C60 exposure at higher exposure concentrations (15 and 30mg/m(3)). C60 was detected in bronchial lymph nodes but the burden was not quantified due to the high variability in the data. C60 concentrations were below the experimental limit of quantitation (ELOQ) in liver, spleen, blood, brain and kidney tissues. These tissue burden data provide information for comparison between nanometer and micrometer sized C60 particle exposure and will aid in the interpretation of toxicity data.


Assuntos
Fulerenos/metabolismo , Pulmão/metabolismo , Microesferas , Nanopartículas/metabolismo , Administração por Inalação , Animais , Brônquios/metabolismo , Feminino , Meia-Vida , Linfonodos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos , Tamanho da Partícula , Ratos , Ratos Wistar , Especificidade da Espécie , Baço/metabolismo , Distribuição Tecidual
6.
Appl Surf Sci ; 359: 911-916, 2015 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-26692601

RESUMO

Surface initiated atom transfer radical polymerization (ATRP) of substituted styrenes leads to rapid synthesis of uniform and thick substituted polystyrene brushes (>100 nm in 1 hour) from gold surface. High growth rates were observed for styrenes substituted with electron withdrawing groups in meta/para positions. The effects seen in surface and solution polymerizations are similar for styrenes with electron withdrawing groups, and for electron donors in ortho and para positions. However, electron donors at meta sites have surprisingly fast growth rates, which may be due to steric inhibition of termination. The overall surface polymerization rates for substituted styrenes was analyzed and found to follow the Hammett relation with ρ = 0.51. The ratio of kp to kt, is as an indicator of the likelihood that a reaction will reach high degrees of polymerization before termination.

7.
ACS Appl Mater Interfaces ; 7(34): 19335-41, 2015 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-26264507

RESUMO

A composite lithium electrolyte composed of polyelectrolyte-grafted nanoparticles and polyethylene glycol dimethyl ether (PEGDME) is synthesized and characterized. Polyanions immobilized by the silica nanoparticles have reduced anion mobility. Composite nanoparticles grafted by poly(lithium 4-styrenesulfonate) only have moderate conductivity at 60 °C. Almost an order increase of the conductivity to ∼10(-6) S/cm is achieved by co-polymerization of the poly(ethylene oxide) methacrylate with sodium 4-styrenesulfonate, which enhances dissociation between lithium cation and polyanion and facilitates lithium ion transfer from the inner part of the polyelectrolyte layer. This composite electrolyte has the potential to suppress lithium dendrite growth and enable the use of lithium metal anode in rechargeable batteries.

8.
Toxicology ; 333: 195-205, 2015 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-25896363

RESUMO

Occupational exposure to cobalt is of widespread concern due to its use in a variety of industrial processes and the occurrence of occupational disease. Due to the lack of toxicity and carcinogenicity data following exposure to cobalt, and questions regarding bioavailability following exposure to different forms of cobalt, the NTP conducted two chronic inhalation exposure studies in rats and mice, one on soluble cobalt sulfate heptahydrate, and a more recent study on insoluble cobalt metal. Herein, we compare and contrast the toxicity profiles following whole-body inhalation exposures to these two forms of cobalt. In general, both forms were genotoxic in the Salmonella T98 strain in the absence of effects on micronuclei. The major sites of toxicity and carcinogenicity in both chronic inhalation studies were the respiratory tract in rats and mice, and the adrenal gland in rats. In addition, there were distinct sites of toxicity and carcinogenicity noted following exposure to cobalt metal. In rats, carcinogenicity was observed in the blood, and pancreas, and toxicity was observed in the testes of rats and mice. Taken together, these findings suggest that both forms of cobalt, soluble and insoluble, appear to be multi-site rodent carcinogens following inhalation exposure.


Assuntos
Cobalto/toxicidade , Neoplasias das Glândulas Suprarrenais/induzido quimicamente , Neoplasias das Glândulas Suprarrenais/patologia , Medula Suprarrenal/efeitos dos fármacos , Medula Suprarrenal/patologia , Animais , Testes de Carcinogenicidade , Cobalto/química , Feminino , Neoplasias Hematológicas/induzido quimicamente , Neoplasias Hematológicas/patologia , Exposição por Inalação , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Testes de Mutagenicidade , Neoplasias Pancreáticas/induzido quimicamente , Neoplasias Pancreáticas/patologia , Ratos Endogâmicos F344 , Sistema Respiratório/efeitos dos fármacos , Sistema Respiratório/patologia , Medição de Risco , Salmonella/efeitos dos fármacos , Salmonella/genética , Solubilidade , Especificidade da Espécie , Testículo/efeitos dos fármacos , Testículo/patologia , Fatores de Tempo , Testes de Toxicidade Crônica
9.
Polym Chem ; 6(8): 1275-1285, 2015 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-25685199

RESUMO

A new class of clickable and biodegradable polylactide was designed and prepared via bulk polymerization of 3,6-dipropargyloxymethyl-1,4-dioxane-2,5-dione (1) which was synthesized from easily accessible propargyloxylactic acid (5). A homopolymer of 1 and random copolymer of 1 with l-lactide were obtained as amorphous materials and exhibit low Tg of 8.5 and 34 °C, respectively, indicating their promising potentials for biomedical applications. The statistical nature of random copolymers was investigated by DSC analysis and 13C NMR spectroscopy, which implies the random distribution of terminal alkyne groups along the back bone of copolymers. The efficient click post-modification of this new class of polylactide with alkyl and mPEG azides affords novel hydrophilic biomaterials, which exhibit reversible thermo-responsive properties as evidenced by their tunable LCST ranging from 22 to 69 °C depending on the balance of the incorporated hydrophilic/hydrophobic side chains. These results indicate the generality of this new class of clickable polylactide in preparing novel smart biomaterials in a simple and efficient manner via click chemistry.

10.
J Org Chem ; 79(20): 9546-55, 2014 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-25255205

RESUMO

A new simple and practical protocol for scalable synthesis of a novel library of propargylated and PEGylated α-hydroxy acids toward the preparation of "clickable" polylactides was described. The overall synthesis starting from readily available propargyl alcohol, bromoacetaldehyde diethyl acetal, and OEGs or PEGs was developed as a convenient procedure with low cost and no need of column chromatographic purification. The terminal alkyne functionality survives from hydrolysis of the corresponding easily accessible cyanohydrin derivatives in methanolic sulfuric acid. Facile desymmetrization, monofunctionalization, and efficient chain-elongation coupling of OEGs further enable the incorporation of OEGs to α-hydroxy acids in a simple and efficient manner. At the end, synthesis of allyloxy lactic acid indicates that an alkene group is also compatible with the developed method.


Assuntos
Alcinos/química , Hidroxiácidos/química , Hidroxiácidos/síntese química , Nitrilas/química , Poliésteres/química , Poliésteres/síntese química , Polietilenoglicóis/química , Propanóis/química , Compostos de Sulfidrila/química , Química Click , Hidrólise , Modelos Moleculares
11.
Beilstein J Org Chem ; 10: 1365-71, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24991290

RESUMO

2-Hydroxy-4-pentynoic acid (1) is a key intermediate towards 'clickable' polylactide which allows for efficient introduction of a broad range of pendant functional groups onto polymers from a single monomer via convenient 'click' chemistry with organic azides. The incorporation of various pendant functional groups could effectively tailor the physicochemical properties of polylactide. The reported synthesis of 1 started from propargyl bromide and ethyl glyoxylate. However, both of starting materials are expensive and unstable; especially, propargyl bromide is shock-sensitive and subjected to thermal explosive decomposition, which makes the preparation of 1 impractical with high cost and high risk of explosion. Herein, we report a simple, economical and safe synthetic route to prepare 1 using cheap and commercially available diethyl 2-acetamidomalonate (4) and propargyl alcohol. The desired product 1 was obtained via alkylation of malonate 4 with propargyl tosylate followed by a one-pot four-step sequence of hydrolysis, decarboxylation, diazotization and hydroxylation of propargylic malonate 5 without work-up of any intermediate.

12.
Nanotoxicology ; 8 Suppl 1: 11-23, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24256152

RESUMO

Engineered nanoparticles are widely used in commercial products, and yet due to the paucity of safety information, there are concerns surrounding potential adverse health effects, especially from inhaled nanoparticles and their putative contribution to allergic airway disease. The objective of this study was to investigate whether size or surface chemistry of engineered nanoparticles can influence the immune enhancing properties of these agents on antigen-specific T cell responses. Ovalbumin (OVA)-derived peptides were presented to T cells by either spleen-derived endogenous antigen presenting cells or a mouse dendritic cell (DC) line, DC2.4. In all models, interferon (IFN)-γ and interleukin (IL)-2 production by CD8(+) or CD4(+) T cells in response to peptide OVA257-264 or OVA323-339, respectively, was measured by flow cytometry. To address the study objective, silica nanoparticles (SNPs) were modified with alkyne-terminated surfaces and appended with polyethylene glycol chains via "click" chemistry. These modified SNPs were resistant to agglomerate in in vitro culture media, suggesting that their modulation of T cell responses is the result of true nanoscale-mediated effects. Under conditions of suboptimal T-cell activation, modified SNPs (up to 10 µg/ml) enhanced the proportion of CD8(+), but not CD4(+), T cells producing IFN-γ and IL-2. Various functional groups (-COOH, -NH2 and -OH) on modified SNPs enhanced IFN-γ and IL-2 production to different levels, with -COOH SNPs being the most effective. Furthermore, 51 nm -COOH SNPs exhibited a greater enhancing effect on the CD8(+) T cell response than other sized particles. Collectively, our results show that modified SNPs can enhance antigen-specific CD8(+) T cell responses, suggesting that certain modified SNPs exhibit potential adjuvant-like properties.


Assuntos
Citocinas/biossíntese , Nanopartículas , Linfócitos T/metabolismo , Animais , Citometria de Fluxo , Espectroscopia de Ressonância Magnética , Camundongos
13.
Biochim Biophys Acta ; 1838(1 Pt B): 429-37, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24060565

RESUMO

Engineered nanomaterials (ENM) have desirable properties that make them well suited for many commercial applications. However, a limited understanding of how ENM's properties influence their molecular interactions with biomembranes hampers efforts to design ENM that are both safe and effective. This paper describes the use of a tethered bilayer lipid membrane (tBLM) to characterize biomembrane disruption by functionalized silica-core nanoparticles. Electrochemical impedance spectroscopy was used to measure the time trajectory of tBLM resistance following nanoparticle exposure. Statistical analysis of parameters from an exponential resistance decay model was then used to quantify and analyze differences between the impedance profiles of nanoparticles that were unfunctionalized, amine-functionalized, or carboxyl-functionalized. All of the nanoparticles triggered a decrease in membrane resistance, indicating nanoparticle-induced disruption of the tBLM. Hierarchical clustering allowed the potency of nanoparticles for reducing tBLM resistance to be ranked in the order amine>carboxyl~bare silica. Dynamic light scattering analysis revealed that tBLM exposure triggered minor coalescence for bare and amine-functionalized silica nanoparticles but not for carboxyl-functionalized silica nanoparticles. These results indicate that the tBLM method can reproducibly characterize ENM-induced biomembrane disruption and can distinguish the BLM-disruption patterns of nanoparticles that are identical except for their surface functional groups. The method provides insight into mechanisms of molecular interaction involving biomembranes and is suitable for miniaturization and automation for high-throughput applications to help assess the health risk of nanomaterial exposure or identify ENM having a desired mode of interaction with biomembranes.


Assuntos
Bicamadas Lipídicas/química , Nanopartículas/química , Fosfatidilcolinas/química , Dióxido de Silício/química , Triglicerídeos/química , Espectroscopia Dielétrica , Luz , Nanopartículas/ultraestrutura , Tamanho da Partícula , Espalhamento de Radiação
14.
Langmuir ; 29(41): 12720-9, 2013 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-24044576

RESUMO

Layer-by-layer adsorption of protonated poly(allylamine) (PAH) and deprotonated poly(N,N-dicarboxymethylallylamine) (PDCMAA) yields thick films with a high density of iminodiacetic acid (IDA) ligands that bind metal ions. When film deposition occurs at pH 3.0, PAH/PDCMAA bilayer thicknesses reach 200 nm, and Cu(2+) binding capacities are ~2.5 mmol per cm(3) of film. (PAH/PDCMAA)10 films deposited at pH 3.0 are 4-8-fold thicker than films formed at pH 5.0, 7.0, or 9.0, presumably because of the low charge density on PDCMAA chains at pH 3.0. However, with normalization to film thickness, all films bind similar amounts of Cu(2+) from pH 4.1 solutions of CuSO4. In micrometer-thick films, equilibration of binding sites with Cu(2+) requires ~4 h due to a low Cu(2+) diffusion coefficient (~2.6 × 10(-12) cm(2)/s). Sorption isotherms determined at several temperatures show that Cu(2+) binding is endothermic with a positive entropy (binding constants increase with increasing temperature), presumably because metal-ion complexation involves displacement of both a proton from IDA and water molecules from Cu(2+). (PAH/PDCMAA)10 films retain their binding capacity over four absorption/elution cycles and may prove useful in metal-ion scavenging, catalysis, and protein binding.


Assuntos
Quelantes/síntese química , Cobre/química , Compostos Organometálicos/síntese química , Adsorção , Quelantes/química , Difusão , Ouro/química , Iminoácidos/química , Estrutura Molecular , Compostos Organometálicos/química , Tamanho da Partícula , Poliaminas/química , Propriedades de Superfície , Temperatura
15.
Part Fibre Toxicol ; 10: 26, 2013 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-23815813

RESUMO

BACKGROUND: With the increase in production and use of engineered nanoparticles (NP; ≤ 100 nm), safety concerns have risen about the potential health effects of occupational or environmental NP exposure. Results of animal toxicology studies suggest that inhalation of NP may cause pulmonary injury with subsequent acute or chronic inflammation. People with chronic respiratory diseases like asthma or allergic rhinitis may be even more susceptible to toxic effects of inhaled NP. Few studies, however, have investigated adverse effects of inhaled NP that may enhance the development of allergic airway disease. METHODS: We investigated the potential of polyethylene glycol coated amorphous silica NP (SNP; 90 nm diameter) to promote allergic airway disease when co-exposed during sensitization with an allergen. BALB/c mice were sensitized by intranasal instillation with 0.02% ovalbumin (OVA; allergen) or saline (control), and co-exposed to 0, 10, 100, or 400 µg of SNP. OVA-sensitized mice were then challenged intranasally with 0.5% OVA 14 and 15 days after sensitization, and all animals were sacrificed a day after the last OVA challenge. Blood and bronchoalveolar lavage fluid (BALF) were collected, and pulmonary tissue was processed for histopathology and biochemical and molecular analyses. RESULTS: Co-exposure to SNP during OVA sensitization caused a dose-dependent enhancement of allergic airway disease upon challenge with OVA alone. This adjuvant-like effect was manifested by significantly greater OVA-specific serum IgE, airway eosinophil infiltration, mucous cell metaplasia, and Th2 and Th17 cytokine gene and protein expression, as compared to mice that were sensitized to OVA without SNP. In saline controls, SNP exposure did cause a moderate increase in airway neutrophils at the highest doses. CONCLUSIONS: These results suggest that airway exposure to engineered SNP could enhance allergen sensitization and foster greater manifestation of allergic airway disease upon secondary allergen exposures. Whereas SNP caused innate immune responses at high doses in non-allergic mice, the adjuvant effects of SNP were found at lower doses in allergic mice and were Th2/Th17 related. In conclusion, these findings in mice suggest that individuals exposed to SNP might be more prone to manifest allergic airway disease, due to adjuvant-like properties of SNP.


Assuntos
Pulmão/efeitos dos fármacos , Nanopartículas/toxicidade , Ovalbumina , Hipersensibilidade Respiratória/induzido quimicamente , Dióxido de Silício/toxicidade , Animais , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/imunologia , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Imunoglobulina E/sangue , Mediadores da Inflamação/metabolismo , Exposição por Inalação/efeitos adversos , Pulmão/imunologia , Pulmão/metabolismo , Linfonodos/efeitos dos fármacos , Linfonodos/imunologia , Camundongos Endogâmicos BALB C , Infiltração de Neutrófilos/efeitos dos fármacos , Tamanho da Partícula , Eosinofilia Pulmonar/sangue , Eosinofilia Pulmonar/induzido quimicamente , Eosinofilia Pulmonar/imunologia , Hipersensibilidade Respiratória/sangue , Hipersensibilidade Respiratória/genética , Hipersensibilidade Respiratória/imunologia , Medição de Risco , Células Th17/efeitos dos fármacos , Células Th17/imunologia , Células Th17/metabolismo , Células Th2/efeitos dos fármacos , Células Th2/imunologia , Fatores de Tempo
16.
ACS Appl Mater Interfaces ; 5(10): 4155-61, 2013 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-23607405

RESUMO

Hole-conducting silica/polymer nanocomposites exhibit interesting physical and chemical properties with important applications in the field of energy storage and hybrid solar cells. Although the conventional strategy of grafting hole-conducting polymer onto the surface of silica nanoparticles is to use in situ oxidative polymerization, a promising alternative of using surface-initiated controlled living radical polymerization has arisen to anchor the polymer on the silica. The resulting silica/polymer nanocomposites from the latter method are more chemically and thermally stable because of the strong covalent bonding compared to the electrostatic interaction from in situ polymerization. The use of these nanocomposites mixed with spiro-MeOTAD (2,2',7,7'-tetrakis(N,N-di-p-methoxyphenylamine)-9,9'-spirobifluorene) as a new hole conductor in the application of solid-state dye-sensitized solar cell (ss-DSSC) is reported here. The power conversion efficiency of this ss-DSSC is higher than the full spiro-MeOTAD ss-DSSC. Notably, the short circuit current improves by 26%. It is explained by large size silica/polymer nanocomposites forming an additional light scattering layer on the top of photoanode. This is the first time a conductive light scattering layer is introduced into ss-DSSC to enhance cell performance.

17.
Langmuir ; 29(9): 2946-54, 2013 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-23351043

RESUMO

In principle, incorporation of comb-like block copolymers in multilayer polyelectrolyte films can both increase film thickness relative to coatings containing linear polymers and provide more swollen films for increased sorption of proteins. In the absence of added salt, alternating adsorption of 5 bilayers of protonated poly(allylamine) (PAH) and comb-like poly(2-hydroxyethyl methacrylate)-graft-poly(acrylic acid) (PHEMA-g-PAA) leads to ∼2-fold thicker coatings than adsorption of PAH and linear PAA, and the difference in the thicknesses of the two coatings increases with the number of bilayers. Moreover, the (PAH/PHEMA-g-PAA)n films sorb 2- to 4-fold more protein than corresponding films prepared with linear PAA, and coatings deposited at pH 3.0 sorb more protein than coatings adsorbed at pH 5.0, 7.0, or 9.0. In fact changes in deposition pH and addition of 0.5 M NaCl to polyelectrolyte adsorption solutions alter protein sorption more dramatically than variations in the constituent polymer architecture. When deposited from 0.5 M NaCl at pH 3.0, both (PAH/PHEMA-g-PAA)5 and (PAH/PAA)5 films increase in thickness more than 400% upon adsorption of lysozyme. These films contain a high concentration of free -COOH groups, and subsequent deprotonation of these groups at neutral pH likely contributes to increased protein binding. Lysozyme sorption stabilizes these films, as without lysozyme films deposited at pH 3.0 from 0.5 M NaCl desorb at neutral pH. Films deposited at pH 9.0 from 0.5 M NaCl are more stable and also bind large amounts of lysozyme. The high binding capacities of these films make them attractive for potential applications in protein isolation or immobilization of enzymes.


Assuntos
Resinas Acrílicas/química , Muramidase/química , Adsorção , Concentração de Íons de Hidrogênio , Modelos Moleculares , Conformação Molecular , Concentração Osmolar , Poli-Hidroxietil Metacrilato/química , Cloreto de Sódio/química
18.
Langmuir ; 28(17): 6885-92, 2012 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-22468687

RESUMO

Layer-by-layer polyelectrolyte adsorption is a simple, convenient method for introducing ion-exchange sites in porous membranes. This study demonstrates that adsorption of poly(acrylic acid) (PAA)-containing films at pH 3 rather than pH 5 increases the protein-binding capacity of such polyelectrolyte-modified membranes 3-6-fold. The low adsorption pH generates a high density of -COOH groups that function as either ion-exchange sites or points for covalent immobilization of metal-ion complexes that selectively bind tagged proteins. When functionalized with nitrilotriacetate (NTA)-Ni(2+) complexes, membranes containing PAA/polyethylenimine (PEI)/PAA films bind 93 mg of histidine(6)-tagged (His-tagged) ubiquitin per cm(3) of membrane. Additionally these membranes isolate His-tagged COP9 signalosome complex subunit 8 from cell extracts and show >90% recovery of His-tagged ubiquitin. Although modification with polyelectrolyte films occurs by simply passing polyelectrolyte solutions through the membrane for as little as 5 min, with low-pH deposition the protein binding capacities of such membranes are as high as for membranes modified with polymer brushes and 2-3-fold higher than for commercially available immobilized metal affinity chromatography (IMAC) resins. Moreover, the buffer permeabilities of polyelectrolyte-modified membranes that bind His-tagged protein are ~30% of the corresponding permeabilities of unmodified membranes, so protein capture can occur rapidly with low-pressure drops. Even at a solution linear velocity of 570 cm/h, membranes modified with PAA/PEI/PAA exhibit a lysozyme dynamic binding capacity (capacity at 10% breakthrough) of ~40 mg/cm(3). Preliminary studies suggest that these membranes are stable under depyrogenation conditions (1 M NaOH).


Assuntos
Resinas Acrílicas/química , Membranas Artificiais , Proteínas/química , Adsorção , Animais , Bovinos , Humanos , Concentração de Íons de Hidrogênio , Hidroxilação , Ácido Nitrilotriacético/análogos & derivados , Ácido Nitrilotriacético/química , Nylons/química , Compostos Organometálicos/química , Permeabilidade , Poliaminas/química , Polietilenoimina/química
19.
J Memb Sci ; 389: 117-125, 2012 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-22287817

RESUMO

Microporous membranes are attractive for protein purification because convection rapidly brings proteins to binding sites. However, the low binding capacity of such membranes limits their applications. This work reports a rapid, aqueous procedure to create highly permeable, polymer brush-modified membranes that bind large amounts of protein. The synthetic method includes a 10-min adsorption of a macroinitiator in a hydroxylated nylon membrane and a subsequent 5-min aqueous atom transfer radical polymerization of 2-(methacryloyloxy)ethyl succinate from the immobilized initiator to form poly(acid) brushes. This procedure likely leads to more swollen, less dense brushes than polymerization from silane initiators, and thus requires less polymer to achieve the same binding capacity. The hydraulic permeability of the poly(acid) membranes is 4-fold higher than that of similar membranes prepared by growing brushes from immobilized silane initiators. These brush-containing nylon membranes bind 120 mg/cm(3) of lysozyme using solution residence times as short as 35 ms, and when functionalized with nitrilotriacetate (NTA)-Ni(2+) complexes, they capture 85 mg/cm(3) of histidine(6)-tagged (His-tagged) Ubiquitin. Additionally the NTA-Ni(2+)-functionalized membranes isolate His-tagged myo-inositol-1-phosphate synthase directly from cell extracts and show >90% recovery of His-tagged proteins.

20.
Macromolecules ; 45(22)2012 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-24293702

RESUMO

Azidopropyl methacrylate (AzPMA), a functional monomer with a pendent azido group, polymerizes from surfaces and provides polymer brushes amenable to subsequent elaboration via click chemistry. In DMF at 50 °C, click reactions between poly(AzPMA) brushes and an alkynylated dye proceed with >90% conversion in a few minutes. However, in aqueous solutions, reaction with an alkyne-containing poly(ethylene glycol) methyl ether (mPEG, Mn=5000) gives <10% conversion after a 12-h reaction at room temperature. Formation of copolymers with AzPMA and polyethylene glycol methyl ether methacrylate (mPEGMA) enables control over the hydrophilicity and functional group density in the copolymer to increase the yield of aqueous click reactions. The copolymers show reaction efficiencies as high as 60%. These studies suggest that for aqueous applications such as bioconjugation via click chemistry, control over brush hydrophilicity is vital.

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