RESUMEN
Inhalation of multiwalled carbon nanotubes (MWCNTs) during their manufacture or incorporation into various commercial products may cause lung inflammation, fibrosis, and oxidative stress in exposed workers. Some workers may be more susceptible to these effects because of differences in their ability to synthesize the major antioxidant and immune system modulator glutathione (GSH). Accordingly, in this study we examined the influence of GSH synthesis and gender on MWCNT-induced lung inflammation in C57BL/6 mice. GSH synthesis was impaired through genetic manipulation of Gclm, the modifier subunit of glutamate cysteine ligase, the rate-limiting enzyme in GSH synthesis. Twenty-four hours after aspirating 25µg of MWCNTs, all male mice developed neutrophilia in their lungs, regardless of Gclm genotype. However, female mice with moderate (Gclm heterozygous) and severe (Gclm null) GSH deficiencies developed significantly less neutrophilia. We found no indications of MWCNT-induced oxidative stress as reflected in the GSH content of lung tissue and epithelial lining fluid, 3-nitrotyrosine formation, or altered mRNA or protein expression of several redox-responsive enzymes. Our results indicate that GSH-deficient female mice are rendered uniquely susceptible to an attenuated neutrophil response. If the same effects occur in humans, GSH-deficient women manufacturing MWCNTs may be at greater risk for impaired neutrophil-dependent clearance of MWCNTs from the lung. In contrast, men may have effective neutrophil-dependent clearance, but may be at risk for lung neutrophilia regardless of their GSH levels.
Asunto(s)
Glutatión/biosíntesis , Nanotubos de Carbono/efectos adversos , Oxidación-Reducción , Estrés Oxidativo , Neumonía/etiología , Neumonía/metabolismo , Animales , Líquido del Lavado Bronquioalveolar , Citocinas/metabolismo , Femenino , Fibrosis/genética , Fibrosis/metabolismo , Regulación de la Expresión Génica , Mediadores de Inflamación/metabolismo , Pulmón/metabolismo , Pulmón/patología , Masculino , Ratones , Ratones Noqueados , Factores SexualesRESUMEN
Shape of engineered nanomaterials (ENMs) can be used as a design handle to achieve controlled manipulation of physicochemical properties. This tailored material property approach necessitates the establishment of relationships between specific ENM properties that result from such manipulations (e.g., surface area, reactivity, or charge) and the observed trend in behavior, from both a functional performance and hazard perspective. In this study, these structure-property-function (SPF) and structure-property-hazard (SPH) relationships are established for nano-cupric oxide (n-CuO) as a function of shape, including nanospheres and nanosheets. In addition to comparing these shapes at the nanoscale, bulk CuO is studied to compare across length scales. The results from comprehensive material characterization revealed correlations between CuO surface reactivity and bacterial toxicity with CuO nanosheets having the highest surface reactivity, electrochemical activity, and antimicrobial activity. While less active than the nanosheets, CuO nanoparticles (sphere-like shape) demonstrated enhanced reactivity compared to the bulk CuO. This is in agreement with previous studies investigating differences across length-scales. To elucidate the underlying mechanisms of action to further explain the shape-dependent behavior, kinetic models applied to the toxicity data. In addition to revealing different CuO material kinetics, trends in observed response cannot be explained by surface area alone. The compiled results contribute to further elucidate pathways toward controlled design of ENMs.
Asunto(s)
Antiinfecciosos/química , Antiinfecciosos/farmacología , Cobre/química , Cobre/farmacología , Nanopartículas/química , Capacidad Eléctrica , Escherichia coli/efectos de los fármacos , Escherichia coli/ultraestructura , Glutatión/metabolismo , Iones , Cinética , Viabilidad Microbiana/efectos de los fármacos , Nanopartículas/ultraestructura , Polvos , Solubilidad , Propiedades de SuperficieRESUMEN
There is a need for new methodologies to quickly assess the presence and reactivity of nanoparticles (NPs) in commercial, environmental, and biological samples since current detection techniques require expensive and complex analytical instrumentation. Here, we investigate a simple and portable colorimetric detection assay that assesses the surface reactivity of NPs, which can be used to detect the presence of NPs, in complex matrices (e.g., environmental waters, serum, urine, and in dissolved organic matter) at as low as part per billion (ppb) or ng/mL concentration levels. Surface redox reactivity is a key emerging property related to potential toxicity of NPs with living cells, and is used in our assays as a key surrogate for the presence of NPs and a first tier analytical strategy toward assessing NP exposures. We detect a wide range of metal (e.g., Ag and Au) and oxide (e.g., CeO2, SiO2, VO2) NPs with a diameter range of 5 to 400 nm and multiple capping agents (tannic acid (TA), polyvinylpyrrolidone (PVP), branched polyethylenimine (BPEI), polyethylene glycol (PEG)). This method is sufficiently sensitive (ppb levels) to measure concentrations typically used in toxicological studies, and uses inexpensive, commercially available reagents.
Asunto(s)
Colorimetría/métodos , Nanopartículas del Metal/química , Catálisis , Colorantes/química , Electrones , Ambiente , Oro/química , Concentración de Iones de Hidrógeno , Límite de Detección , Azul de Metileno/química , Tamaño de la Partícula , Polietilenglicoles/química , Povidona/química , Taninos/química , AguaRESUMEN
Carbon nanotubes (CNTs) have one of the highest production volumes among carbonaceous engineered nanoparticles (ENPs) worldwide and are have potential uses in applications including biomedicine, nanocomposites, and energy conversion. However, CNTs possible widespread usage and associated likelihood for biological exposures have driven concerns regarding their nanotoxicity and ecological impact. In this work, we probe the responses of planar suspended lipid bilayer membranes, used as model cell membranes, to functionalized multi-walled carbon nanotubes (MWCNT), CdSe/ZnS quantum dots, and a control organic compound, melittin, using an electrophysiological measurement platform. The electrophysiological measurements show that MWCNTs in a concentration range of 1.6 to 12 ppm disrupt lipid membranes by inducing significant transmembrane current fluxes, which suggest that MWCNTs insert and traverse the lipid bilayer membrane, forming transmembrane carbon nanotubes channels that allow the transport of ions. This paper demonstrates a direct measurement of ion migration across lipid bilayers induced by CNTs. Electrophysiological measurements can provide unique insights into the lipid bilayer-ENPs interactions and have the potential to serve as a preliminary screening tool for nanotoxicity.
RESUMEN
Lipid bilayers are biomembranes common to cellular life and constitute a continuous barrier between cells and their environment. Understanding the interaction of engineered nanomaterials (ENMs) with lipid bilayers is an important step toward predicting subsequent biological effects. In this study, we assess the effect of varying the surface functionality and concentration of 10-nm-diameter gold (Au) and titanium dioxide (TiO(2)) ENMs on the disruption of negatively charged lipid bilayer vesicles (liposomes) using a dye-leakage assay. Our findings show that Au ENMs having both positive and negative surface charge induce leakage that reaches a steady state after several hours. Positively charged particles with identical surface functionality and different core compositions show similar leakage effects and result in faster and greater leakage than negatively charged particles, which suggests that surface functionality, not particle core composition, is a critical factor in determining the interaction between ENMs and lipid bilayers. The results suggest that particles permanently adsorb to bilayers and that only one positively charged particle is required to disrupt a liposome and trigger the leakage of its entire contents in contrast to mellitin molecules, the most widely studied membrane lytic peptide, which requires hundred of molecules to generate leakage.
Asunto(s)
Membrana Celular/efectos de los fármacos , Nanopartículas/química , Nanopartículas/toxicidad , Liposomas Unilamelares/química , Membrana Celular/química , Membrana Celular/metabolismo , Ingeniería , Oro/química , Oro/toxicidad , Cinética , Meliteno/química , Meliteno/metabolismo , Tamaño de la Partícula , Fosfatidilcolinas/química , Propiedades de Superficie , Titanio/química , Titanio/toxicidad , Liposomas Unilamelares/metabolismoRESUMEN
Lipid bilayers are biomembranes common to cellular life and constitute a continuous barrier between cells and their environment. Understanding the interaction of nanoparticles with lipid bilayers is an important step toward predicting subsequent biological effects. In this study, we assessed the affinity of functionalized gold nanoparticles (Au NPs) with sizes from 5 to 100 nm to lipid bilayers by determining the Au NP distribution between aqueous electrolytes and lipid bilayers. The Au NP distribution to lipid bilayers reached an apparent steady state in 24 h with smaller Au NPs distributing onto lipid bilayers more rapidly than larger ones. Au NPs distributed to lipid bilayers to a larger extent at lower pH. Tannic acid-functionalized Au NPs exhibited greater distribution to lipid bilayers than polyvinylpyrrolidone-functionalized Au NPs of the same size. Across the various Au NP sizes, we measure the lipid bilayer-water distribution coefficient (K(lipw) = C(lip)/C(w)) as 450 L/kg lipid, which is independent of dosimetric units. This work suggests that the nanoparticle-cell membrane interaction is dependent on solution chemistry and nanoparticle surface functionality. The K(lipw) value may be used to predict the affinity of spherical Au NPs across a certain size range toward lipid membranes.
Asunto(s)
Membrana Celular/química , Oro/química , Membrana Dobles de Lípidos/química , Nanopartículas del Metal/química , Adsorción , Concentración de Iones de Hidrógeno , Microscopía Electrónica de Rastreo , Microscopía Electrónica de Transmisión , Tamaño de la Partícula , Povidona , Análisis Espectral , Taninos , Agua/químicaRESUMEN
We present a method of photochemical modification of an optical fiber tip with a silver nanoparticle film. The deposited silver nanoparticle film displays alternating light and dark circles, which are similar to a radial diffraction pattern. The modified optical fiber is examined as a chemical sensor for in situ detection. The modified fibers show excellent SERS activity, a low limit of detection (LOD), and good reproducibility. The maximum SERS activity of the sensor was achieved within 5.0 min of deposition. Thus, the method is also quite rapid.