TY - JOUR AB - Cellulose nanocrystals (CNCs) exhibit advantageous chemical and mechanical properties that render them attractive for a wide range of applications. During the life-cycle of CNC containing materials the nanocrystals could be released and become airborne, posing a potential inhalatory exposure risk towards humans. Absent reliable and dose-controlled models that mimic this exposure in situ is a central issue in gaining an insight into the CNC-lung interaction. Here, an Air Liquid Interface Cell Exposure system (ALICE), previously designed for studies of spherical nanoparticles, was used for the first time to establish a realistic physiological exposure test method for inhaled fiber shaped nano-objects; in this case, CNCs isolated from cotton. Applying a microscopy based approach the spatially homogenous deposition of CNCs was demonstrated as a prerequisite of the functioning of the ALICE. Furthermore, reliability and controllability of the system to nebulise high aspect ratio nanomaterials (HARN, e.g. CNCs) was shown. This opens the potential to thoroughly investigate the inhalatory risk of CNCs in vitro using a realistic exposure system. © IOP Publishing Ltd 2013. AU - Endes, C.* AU - Müller, S.* AU - Schmid, O. AU - Vanhecke, D.* AU - Foster, E.J.* AU - Petri-Fink, A.* AU - Rothen-Rutishauser, B.* AU - Weder, C.* AU - Clift, M.J.D.* C1 - 26136 C2 - 32087 TI - Risk assessment of released cellulose nanocrystals-mimicking inhalatory exposure. JO - J. Phys. Conf. Ser. VL - 429 IS - 1 PY - 2013 SN - 1742-6588 ER - TY - JOUR AB - The presence of high-Z materials adjacent to soft tissues, when submitted to irradiation, locally enhances the absorbed dose in these tissues. This effect is due to the outscattering of photoelectrons from the high-Z materials. The aim of the present work was to measure the absorbed dose enhancement caused by gold foils on polymeric gel. AU - Afonso, L.C. AU - Greiter, M. AU - Schoefer, F. AU - Hoeschen, C. C1 - 7410 C2 - 29706 SP - 457-461 TI - Dose enhancement caused by gold foils on polymer gels. JO - J. Phys. Conf. Ser. VL - 250 PB - IOP Publishing Ltd PY - 2010 SN - 1742-6588 ER - TY - JOUR AB - Nanotechnology is a broad, revolutionary field with promising advantages for new medicine. In this context the rapid development and improvement of so called nanocarriers is of high pharmaceutical interest and some devices are already on the market. In our project we aim to develop well characterized nanoscaled drug delivery systems for an inhalative application. To this end, we focus on the most adverse side-effects within the lung, the cytotoxic and the proinflammatory responses to these nanoparticles (NPs). Before performing any animal experiments, we start with an in vitro screening for analyzing the cytotoxic and proinflammatory effects of the investigated particles on two murine lung target cell lines, the alveolar epithelial like typ II cell line (LA4) and the alveolar macrophage cell line (MH-S). Three different endpoints were estimated, (i) cellular metabolic activity, determined by the WST-1 assay, (ii) membrane integrity, by detection of LDH release and hemolytic activity, and (iii) secretion of inflammatory mediators. To analyze the relative particle toxicity we choose two reference particles as benchmarks, (i) fine a-quartz, and (ii) ultrafine ZnO particles. The investigation of dose-response and kinetics of proinflammatory and toxic effects caused to the named cell lines provide an insight to a close evaluation of our cell based screening strategy. oc-quartz is well known for its inflammatory and toxic potential caused by inhalation, and nanosized ZnO particles - used in a broad field of nanotechnology like electronics, but also cosmetics and pharmaceuticals - is to a high degree cytotoxic and proinflammatory in vitro. Preliminary experiments indicated not only particle and cell specific inflammatory responses, but also different susceptibilities of the cell types being exposed to our benchmark particles regarding their size and surface activities. Exposure to the ?m-sized a-quartz particles affected the viability of epithelia cells less than that of macrophages, pointing to the impact of particle uptake by phagocytosis. In contrast, the nanosized ZnO particles caused much stronger decrease in cell viability and higher levels of LDH in the macrophage cell line compared to epithelial cells, even though the hemolytic activity was much higher for the a-quartz particles than for the nanosized ZnO. For the proinflammatory effects, we observed a clear dose-dependent release of acute phase cytokines (TNF-?, IL-6, G-CSF> CXCL10>CCL2) for both alveolar cell lines after Min-U-Sil exposure. After ZnO treatment the cytokine responses were negligible compare to control cells. In conclusion, our data attach value to the use of different cell types to detect different pathways of toxicity generated by different particle properties. Therefore, we will establish both lung target cell lines for an in vitro screening to analyze proinflammatory and cytotoxicity effects of nanocarriers. The implementation of the two reference particles facilitate the validated classification of the cytotoxic responses caused by the NPs investigated. AU - Beyerle, A. AU - Schulz, S. AU - Kissel, T.* AU - Stöger, T. C1 - 1135 C2 - 26339 TI - Screening strategy to avoid toxicological hazards of inhaled nanoparticles for drug delivery: The use of a-quartz and nano zinc oxide particles as benchmark. JO - J. Phys. Conf. Ser. VL - 151 PB - IOP Publishing Ltd PY - 2009 SN - 1742-6588 ER - TY - JOUR AB - The deposition sites of inhaled aerosols in the gas-exchange region of the lung represent one of the key parameters needed for the understanding of the interaction between these particles and lung tissue. In order to develop a method for three-dimensional imaging of sub-micron particles in lung tissue we applied gold particles (200 and 700 nm) to rat lungs by intratracheal instillation. The samples were scanned at TOMCAT, the beamline for TOmographic Microscopy and Coherent rAdiology experimenTs at the Swiss Light Source. The 200 nm particles were slightly below the detection capabilities of TOMCAT. Therefore, their localization was obtained only by electron microscopy. At a voxel size of 350 nm we observed single and clustered gold particles (700 nm) in alveoli, alveolar ducts, and small bronchioli. The locations of the gold particles were veri_ed by transmission electron microscopical serial sections. We observed a very high correlation between these two imaging modalities. We conclude that a combination of x-ray tomographic microscopy and electron microscopy allows the full unrestricted 3D localization of particles smaller than the resolution of x-ray tomographic microscopy. We are planning to use this method for the verification of the simulation of particle deposition in the airway tree. AU - Haberthür, D.* AU - Semmler-Behnke, M. AU - Takenaka, S. AU - Kreyling, W.G. AU - Stampanoni, M.* AU - Tsuda, A.* AU - Schittny, J.C.* C1 - 1111 C2 - 26793 TI - Multimodal imaging for the detection of sub-micron particles in the gas-exchange region of the mammalian lung. JO - J. Phys. Conf. Ser. VL - 186 PB - IOP Publishing Ltd PY - 2009 SN - 1742-6588 ER - TY - JOUR AB - Nanoparticles exhibit properties different from those of the same bulk materials leading to unknown toxicological implications that have evoked concern for (1) occupational, (2) consumer and (3) environmental safety. The current work utilizes epidemiological and toxicological data for screening level assessment of these risks using various suggested health relevant dose metrics (mass, particle number and surface area) to (i) quantify the potential risk levels and to (ii) compare the properties of these alternative risk assessment methods. AU - Hänninen, O. AU - Brüske, I. AU - Loh, M.* AU - Stöger, T. AU - Kreyling, W.G. AU - Schmid, O. AU - Peters, A. C1 - 943 C2 - 26462 TI - Estimation of health risks and safety margins due to inhalation of ultrafine particles and nanoparticles in selected occupational, consumer and environmental settings. JO - J. Phys. Conf. Ser. VL - 170 IS - 1 PB - IOP Publishing Ltd PY - 2009 SN - 1742-6588 ER - TY - JOUR AB - The aim of this work is to elucidate the mechanisms involved in the morphological adaptation and regulation of macrophages in the presence of internalised materials. This development will accelerate the toxicology assessment of novel nanomaterials and subsequently reduce their environmental and health exposure. For this purpose, we adapted our established in vitro culture system to investigate and measure cell shape changes with and without functionalized carbon nanotubes (CNTs). Two nanomaterials, such as fluorescent polystyrene (PS) beads and functionalized CNTs, were employed to track the material location under confocal microscopy, light microscopy and Transmission Electron Microscopy (TEM). It was found that particles equally spread throughout the entire cytoplasm in spherical macrophage; whereas when macrophages where forced to adhere to the substrate, via fibronectin coating, the accumulation of particles and tubes was limited to the vicinity of the nucleus due to the modified cellular micro architecture. TEM analysis also confirmed these findings and demonstrated that CNTs of about 5 |am laid at the bottom of adherent cells. Therefore, this cell shape analysis and manipulation may result very important for the quantification of internalised novel materials with high aspect ratio like nanotubes, nanorods and nanowires. AU - Tian, F. AU - Prina-Mello, A.* AU - Estrada, G.G. AU - Beyerle, A. AU - Kreyling, W.G. AU - Stöger, T. C1 - 1322 C2 - 26341 TI - Cell shape imaging analysis: A fast and reliable technique for the investigation of internalised carbon nanotubes in flat macrophages. JO - J. Phys. Conf. Ser. VL - 151 PB - IOP Publishing Ltd PY - 2009 SN - 1742-6588 ER - TY - JOUR AB - This work evaluates the effects of patient size on radiation dose from simulation imaging studies such as four-dimensional computed tomography (4DCT) and kilovoltage cone-beam computed tomography (kV-CBCT). 4DCT studies are scans that include temporal information, frequently incorporating highly over-sampled imaging series necessary for retrospective sorting as a function of respiratory phase. This type of imaging study can result in a significant dose increase to the patient due to the slower table speed as compared with a conventional axial or helical scan protocol. Kilovoltage cone-beam imaging is a relatively new imaging technique that requires an on-board kilovoltage x-ray tube and a flat-panel detector. Instead of porting individual reference fields, the kV tube and flat-panel detector are rotated about the patient producing a cone-beam CT data set (kV-CBCT). To perform these investigations, we used Monte Carlo simulation methods with detailed models of adult patients and virtual source models of multidetector computed tomography (MDCT) scanners. The GSF family of three-dimensional, voxelized patient models, were implemented as input files using the Monte Carlo code MCNPX. The adult patient models represent a range of patient sizes and have all radiosensitive organs previously identified and segmented. Simulated 4DCT scans of each voxelized patient model were performed using a multi-detector CT source model that includes scanner specific spectra, bow-tie filtration, and helical source path. Standard MCNPX tally functions were applied to each model to estimate absolute organ dose based upon an air-kerma normalization measurement for nominal scanner operating parameters. AU - DeMarco, J.J.* AU - McNitt-Gray, M.F.* AU - Cagnon, C.H.* AU - Angel, E.* AU - Agazaryan, N. AU - Zankl, M. C1 - 1136 C2 - 26340 TI - Evaluation of patient dose using a virtual CT scanner: Applications to 4DCT simulation and Kilovoltage cone-beam imaging. JO - J. Phys. Conf. Ser. VL - 102 IS - 1 PB - IOP Publishing Ltd PY - 2008 SN - 1742-6588 ER - TY - JOUR AU - Ballarini, F.* AU - Alloni, D.* AU - Battistoni, G.* AU - Cerutti, F.* AU - Ferrari, A.* AU - Gadioli, E.* AU - Garzelli, M.V.* AU - Liotta., M.* AU - Mairani, A.* AU - Ottolenghi, A.* AU - Paretzke, H.G. AU - Parini, V.* AU - Pelliccioni, M.* AU - Pinsky, L.* AU - Scannicchio, D.* AU - Trovati, S.* AU - Zankl, M. C1 - 5695 C2 - 23832 SP - 135-142 TI - Modelling human exposure to space radiation with different shielding: The FLUKA code coupled with anthropomorphic phantoms. JO - J. Phys. Conf. Ser. VL - 41 PY - 2006 SN - 1742-6588 ER -