Pulmonary toxicity of synthetic amorphous silica–effects of porosity and copper oxide doping

Materials can be modified for improved functionality. Our aim was to test whether pulmonary toxicity of silica nanomaterials is increased by the introduction of: a) porosity; and b) surface doping with CuO; and whether c) these modifications act synergistically. Mice were exposed by intratracheal instillation and for some doses also oropharyngeal aspiration to: 1) solid silica 100 nm; 2) porous silica 100 nm; 3) porous silica 100 nm with CuO doping; 4) solid silica 300 nm; 5) porous silica 300 nm; 6) solid silica 300 nm with CuO doping; 7) porous silica 300 nm with CuO doping; 8) CuO nanoparticles 9.8 nm; or 9) carbon black Printex 90 as benchmark. Based on a pilot study, dose levels were between 0.5 and 162 µg/mouse (0.2 and 8.1 mg/kg bw). Endpoints included pulmonary inflammation (neutrophil numbers in bronchoalveolar fluid), acute phase response, histopathology, and genotoxicity assessed by the comet assay, micronucleus test, and the gamma-H2AX assay. The porous silica materials induced greater pulmonary inflammation than their solid counterparts. A similar pattern was seen for acute phase response induction and histologic changes. This could be explained by a higher specific surface area per mass unit for the most toxic particles. CuO doping further increased the acute phase response normalized according to the deposited surface area. We identified no consistent evidence of synergism between surface area and CuO doping. In conclusion, porosity and CuO doping each increased the toxicity of silica nanomaterials and there was no indication of synergy when the modifications co-occurred

In vivo-induced size transformation of cerium oxide nanoparticles in both lung and liver does not affect long-term hepatic accumulation following pulmonary exposure

<div><p>Recent findings show that cerium oxide (CeO₂) nanoparticles may undergo <i>in vivo</i>-induced size transformation with the formation of smaller particles that could result in a higher translocation following pulmonary exposure compared to virtually insoluble particles, like titanium dioxide (TiO₂). Therefore, we compared liver deposition of CeO₂ and TiO₂ nanoparticles of similar primary sizes 1, 28 or 180 days after intratracheal instillation of 162 μg of NPs in female C57BL/6 mice. Mice exposed to 162 μg CeO₂ or TiO₂ nanoparticles by intravenous injection or oral gavage were included as reference groups to assess the amount of NPs that reach the liver bypassing the lungs and the translocation of NPs from the gastrointestinal tract to the liver, respectively. Pulmonary deposited CeO₂ nanoparticles were detected in the liver 28 and 180 days post-exposure and TiO₂ nanoparticles 180 days post-exposure as determined by darkfield imaging and by the quantification of Ce and Ti mass concentration by inductively coupled plasma-mass spectrometry (ICP-MS). Ce and Ti concentrations increased over time and 180 days post-exposure the translocation to the liver was 2.87 ± 3.37% and 1.24 ± 1.98% of the initial pulmonary dose, respectively. Single particle ICP-MS showed that the size of CeO₂ nanoparticles in both lung and liver tissue decreased over time. No nanoparticles were detected in the liver following oral gavage. Our results suggest that pulmonary deposited CeO₂ and TiO₂ nanoparticles translocate to the liver with similar calculated translocation rates despite their different chemical composition and shape. The observed particle size distributions of CeO₂ nanoparticles indicate <i>in vivo</i> processing over time both in lung and liver. The fact that no particles were detected in the liver following oral exposure showed that direct translocation of nanoparticles from lung to the systemic circulation was the most important route of translocation for pulmonary deposited particles.</p></div

Tailoring 3D single-walled carbon nanotubes anchored to indium tin oxide for natural cellular uptake and intracellular sensing.

The ability to monitor intracellular events in real time is paramount to advancing fundamental biological and clinical science. We present the first demonstration of a direct interface of vertically aligned single-walled carbon nanotubes (VASWCNTs) with eukaryotic cells, RAW 264.7 mouse macrophage cell line. The cells were cultured on indium tin oxide with VASWCNTs. VASWCNTs entered the cells naturally without application of any external force and were shown to sense the intracellular presence of a redox active moiety, methylene blue. The technology developed provides an alluring platform to enable electrochemical study of an intracellular environment

Mapping the Complex Morphology of Cell Interactions with Nanowire Substrates Using FIB-SEM

Using high resolution focused ion beam scanning electron microscopy (FIB-SEM) we study the details of cell-nanostructure interactions using serial block face imaging. 3T3 Fibroblast cellular monolayers are cultured on flat glass as a control surface and on two types of nanostructured scaffold substrates made from silicon black (Nanograss) with low- and high nanowire density. After culturing for 72 hours the cells were fixed, heavy metal stained, embedded in resin, and processed with FIB-SEM block face imaging without removing the substrate. The sample preparation procedure, image acquisition and image post-processing were specifically optimised for cellular monolayers cultured on nanostructured substrates. Cells display a wide range of interactions with the nanostructures depending on the surface morphology, but also greatly varying from one cell to another on the same substrate, illustrating a wide phenotypic variability. Depending on the substrate and cell, we observe that cells could for instance: break the nanowires and engulf them, flatten the nanowires or simply reside on top of them. Given the complexity of interactions, we have categorised our observations and created an overview map. The results demonstrate that detailed nanoscale resolution images are required to begin understanding the wide variety of individual cells' interactions with a structured substrate. The map will provide a framework for light microscopy studies of such interactions indicating what modes of interactions must be considered

Differences in inflammation and acute phase response but similar genotoxicity in mice following pulmonary exposure to graphene oxide and reduced graphene oxide

We investigated toxicity of 2-3 layered >1 μm sized graphene oxide (GO) and reduced graphene oxide (rGO) in mice following single intratracheal exposure with respect to pulmonary inflammation, acute phase response (biomarker for risk of cardiovascular disease) and genotoxicity. In addition, we assessed exposure levels of particulate matter emitted during production of graphene in a clean room and in a normal industrial environment using chemical vapour deposition. Toxicity was evaluated at day 1, 3, 28 and 90 days (18, 54 and 162 μg/mouse), except for GO exposed mice at day 28 and 90 where only the lowest dose was evaluated. GO induced a strong acute inflammatory response together with a pulmonary (Serum-Amyloid A, Saa3) and hepatic (Saa1) acute phase response. rGO induced less acute, but a constant and prolonged inflammation up to day 90. Lung histopathology showed particle agglomerates at day 90 without signs of fibrosis. In addition, DNA damage in BAL cells was observed across time points and doses for both GO and rGO. In conclusion, pulmonary exposure to GO and rGO induced inflammation, acute phase response and genotoxicity but no fibrosis

Nanopack Deliverable 6.2: Title: Manuscript with physico-chemical characterisation of HNTs and HNT hazard characterization

report for&nbsp;Manuscript with physico-chemical characterisation of HNTs and HNT hazard&nbsp;characterization</p

Des espions partout ! En Lorraine et en Alsace avant la Grande Guerre

International audienceParfois rocambolesque, souvent dramatique, l’histoire vraie de ces gens simples, dans un contexte politique troublé, préparait le choc d’août 1914. Si quelques noms sont restés : Charles Appell, Karl Zahn, Alain Gerber… l’affaire Schnaebele aura exacerbé durablement la méfiance qui prévalait alors entre les pays “frères” ennemis.Alors pratiqué dans l’amateurisme, le renseignement, en temps de guerre ou de paix, est maintenant jugé vital pour la sécurité des pays…Avant 1914, de part et d’autre de la nouvelle frontière, la Lorraine et l’Alsace furent des hauts lieux de l’espionnage, conséquence de la défaite française de 1870, deux générations d’agents secrets vont s’y affronter jusqu’à l’inéluctable conflit. Pour quelques francs ou quelques marks, pour laver l’affront ou pour se rêver une double vie, ces voisins, que chacun soupçonnait “d’en être”, étaient ouvriers, paysans ou commerçants… Ces anonymes manipulés furent broyés par des enjeux qui les dépassaient, finissant en prison, déportés, certains perdant la vie pour une photo de la construction d’un fort ou le plan d’un nouveau fusil Lebel transmis à l’ennemi