The Stability of Silver Nanoparticles in a Model of Pulmonary Surfactant

Leo, Bey Fen; Chen, Shu; Kyo, Yoshihiko; Herpoldt, Karla-Luise; Terrill, Nicholas J.; Dunlop, Iain E.; McPhail, David S.; Shaffer, Milo S. P.; Schwander, Stephan; Gow, Andrew J.; Zhang, Junfeng Jim; Chung, Kian Fan; Tetley, Teresa D.; Porter, Alexandra E.; Ryan, Mary P.

doi:10.1021/es403377p

Cited by 102 publications

(133 citation statements)

References 68 publications

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“…Surfactant components are known to opsonize bacteria and may also bind to inhaled particles 40−42 and thus affect how a cell recognizes and interacts with a nanoparticle. To investigate this, we preincubated nanoparticles with human lung lining liquid (collected via bronchoalveolar lavage) for 30 min prior to cell exposure.…”

Section: Resultsmentioning

confidence: 99%

Critical Determinants of Uptake and Translocation of Nanoparticles by the Human Pulmonary Alveolar Epithelium

et al. 2014

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The ability to manipulate the size and surface properties of nanomaterials makes them a promising vector for improving drug delivery and efficacy. Inhalation is a desirable route of administration as nanomaterials preferentially deposit in the alveolar region, a large surface area for drug absorption. However, as yet, the mechanisms by which particles translocate across the alveolar epithelial layer are poorly understood. Here we show that human alveolar type I epithelial cells internalize nanoparticles, whereas alveolar type II epithelial cells do not, and that nanoparticles translocate across the epithelial monolayer but are unable to penetrate the tight junctions between cells, ruling out paracellular translocation. Furthermore, using siRNA, we demonstrate that 50 nm nanoparticles enter largely by passive diffusion and are found in the cytoplasm, whereas 100 nm nanoparticles enter primarily via clathrin- and also caveolin-mediated endocytosis and are found in endosomes. Functionalization of nanoparticles increases their uptake and enhances binding of surfactant which further promotes uptake. Thus, we demonstrate that uptake and translocation across the pulmonary epithelium is controlled by alveolar type I epithelial cells, and furthermore, we highlight a number of factors that should be considered when designing new nanomedicines in order to improve drug delivery to the lung.

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Section: Resultsmentioning

confidence: 99%

Critical Determinants of Uptake and Translocation of Nanoparticles by the Human Pulmonary Alveolar Epithelium

et al. 2014

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“…12,28,29 The confounding influences of these factors can make it difficult to compare dissolution data and biological impacts 30 reported in the literature as a) Electronic mail: don.baer@pnnl.gov demonstrated by the wide variation in the amounts of Ag observed to dissolve during in-vitro studies with a range of seemingly inconsistent biological impacts. 6,25,[31][32][33][34][35][36][37] After testing several AgNPs, Matzke et al 18 found no clear relationship between toxicity and different particle shapes, sizes, or coatings. 18 They suggest an "intricate interplay between particle characteristics and the media in which the tests are carried out."…”

Section: Introductionmentioning

confidence: 99%

Comparison of 20 nm silver nanoparticles synthesized with and without a gold core: Structure, dissolution in cell culture media, and biological impact on macrophages

et al. 2015

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Widespread use of silver nanoparticles raises questions of environmental and biological impact. Many synthesis approaches are used to produce pure silver and silver-shell gold-core particles optimized for specific applications. Since both nanoparticles and silver dissolved from the particles may impact the biological response, it is important to understand the physicochemical characteristics along with the biological impact of nanoparticles produced by different processes. The authors have examined the structure, dissolution, and impact of particle exposure to macrophage cells of two 20 nm silver particles synthesized in different ways, which have different internal structures. The structures were examined by electron microscopy and dissolution measured in Rosewell Park Memorial Institute media with 10% fetal bovine serum. Cytotoxicity and oxidative stress were used to measure biological impact on RAW 264.7 macrophage cells. The particles were polycrystalline, but 20 nm particles grown on gold seed particles had smaller crystallite size with many high-energy grain boundaries and defects, and an apparent higher solubility than 20 nm pure silver particles. Greater oxidative stress and cytotoxicity were observed for 20 nm particles containing the Au core than for 20 nm pure silver particles. A simple dissolution model described the time variation of particle size and dissolved silver for particle loadings larger than 9 μg/ml for the 24-h period characteristic of many in-vitro studies.

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“…Several studies have been conducted investigating the dissolution of Ag ENPs in artificial body fluids such as fluids representing the environment of the stomach, blood and airways (Stebounova et al, 2011a;Leo et al, 2013). Leo et al (2013) studied the effect of a model pulmonary surfactant on Ag ENPs, and showed a decrease in the kinetics of Ag ENP dissolution and of their aggregation.…”

Section: Introductionmentioning

confidence: 99%

“…Leo et al (2013) studied the effect of a model pulmonary surfactant on Ag ENPs, and showed a decrease in the kinetics of Ag ENP dissolution and of their aggregation. Although there are published data on Ag localization and speciation in plants exposed to Ag ENPs (Larue et al, 2014), equivalent data on animal cells and tissues after Ag ENP exposure is lacking.…”

Section: Introductionmentioning

confidence: 99%

Lung distribution, quantification, co-localization and speciation of silver nanoparticles after lung exposure in mice

et al. 2015

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Large knowledge gaps still exist on the toxicological mechanisms of silver (Ag) engineered nanoparticles (ENPs); a comprehensive understanding of the sources, biodistribution, toxicity and transformation of Ag ENPs along their life cycle and after transfer in living organisms is needed. In a previous study, mice were pulmonary exposed to Ag ENPs and local (lung) and systemic toxic effects together with biodistribution to organs including heart, liver, spleen and kidney were investigated. Here, Ag lung distribution, local concentration, co-localization with other elements such as Fe, Cu and S, and speciation were determined after lung exposure to Ag ENPs using micro X-ray fluorescence (μXRF), micro X-ray absorption near edge structure spectroscopy (μXANES) and micro proton-induced X-ray emission (μPIXE) techniques. We found that approximately a quarter of all macrophages in the lumen of the airways contained ENPs. High local concentrations of Ag were also detected in the lung tissue, probably phagocytized by macrophages. The largest part of the ENPs was dissolved and complexed to thiol-containing molecules. Increased concentrations of Fe and Cu observed in the Ag-rich spots suggest that these molecules are metallothioneins (MTs). These results give more insights on the behavior of Ag ENPs in the lung in vivo and will help in the understanding of the toxicological mechanisms of Ag ENPs.

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The Stability of Silver Nanoparticles in a Model of Pulmonary Surfactant

Cited by 102 publications

References 68 publications

Critical Determinants of Uptake and Translocation of Nanoparticles by the Human Pulmonary Alveolar Epithelium

Critical Determinants of Uptake and Translocation of Nanoparticles by the Human Pulmonary Alveolar Epithelium

Comparison of 20 nm silver nanoparticles synthesized with and without a gold core: Structure, dissolution in cell culture media, and biological impact on macrophages

Lung distribution, quantification, co-localization and speciation of silver nanoparticles after lung exposure in mice

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