| 1. |
- Cronholm, Pontus, et al.
(författare)
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Intracellular Uptake and Toxicity of Ag and CuO Nanoparticles : A Comparison Between Nanoparticles and their Corresponding Metal Ions
- 2013
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Ingår i: Small. - : Wiley. - 1613-6810 .- 1613-6829. ; 9:7, s. 970-982
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Tidskriftsartikel (refereegranskat)abstract
- An increased understanding of nanoparticle toxicity and its impact on human health is essential to enable a safe use of nanoparticles in our society. The aim of this study is to investigate the role of a Trojan horse type mechanism for the toxicity of Ag-nano and CuO-nano particles and their corresponding metal ionic species (using CuCl2 and AgNO3), i.e., the importance of the solid particle to mediate cellular uptake and subsequent release of toxic species inside the cell. The human lung cell lines A549 and BEAS-2B are used and cell death/membrane integrity and DNA damage are investigated by means of trypan blue staining and the comet assay, respectively. Chemical analysis of the cellular dose of copper and silver is performed using atomic absorption spectroscopy. Furthermore, transmission electron microscopy, laser scanning confocal microscopy, and confocal Raman microscopy are employed to study cellular uptake and particle-cell interactions. The results confirm a high uptake of CuO-nano and Ag-nano compared to no, or low, uptake of the soluble salts. CuO-nano induces both cell death and DNA damage whereas CuCl2 induces no toxicity. The opposite is observed for silver, where Ag-nano does not cause any toxicity, whereas AgNO3 induces a high level of cell death. In conclusion: CuO-nano toxicity is predominantly mediated by intracellular uptake and subsequent release of copper ions, whereas no toxicity is observed for Ag-nano due to low release of silver ions within short time periods.
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| 2. |
- Elihn, Karine, et al.
(författare)
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Cellular Dose of Partly Soluble Cu Particle Aerosols at the Air-Liquid Interface Using an In Vitro Lung Cell Exposure System
- 2013
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Ingår i: Journal of Aerosol Medicine. - : Mary Ann Liebert Inc. - 1941-2711 .- 1941-2703. ; 26:2, s. 84-93
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is currently a need to develop and test in vitro systems for predicting the toxicity of nanoparticles. One challenge is to determine the actual cellular dose of nanoparticles after exposure. Methods: In this study, human epithelial lung cells (A549) were exposed to airborne Cu particles at the air-liquid interface (ALI). The cellular dose was determined for two different particle sizes at different deposition conditions, including constant and pulsed Cu aerosol flow. Results: Airborne polydisperse particles with a geometric mean diameter (GMD) of 180nm [geometric standard deviation (GSD) 1.5, concentration 10(5) particles/mL] deposited at the ALI yielded a cellular dose of 0.4-2.6 mu g/cm(2) at pulsed flow and 1.6-7.6 mu g/cm(2) at constant flow. Smaller polydisperse particles in the nanoregime (GMD 80 nm, GSD 1.5, concentration 10(7) particles/mL) resulted in a lower cellular dose of 0.01-0.05 mu g/cm(2) at pulsed flow, whereas no deposition was observed at constant flow. Exposure experiments with and without cells showed that the Cu particles were partly dissolved upon deposition on cells and in contact with medium. Conclusions: Different cellular doses were obtained for the different Cu particle sizes (generated with different methods). Furthermore, the cellular doses were affected by the flow conditions in the cell exposure system and the solubility of Cu. The cellular doses of Cu presented here are the amount of Cu that remained on the cells after completion of an experiment. As Cu particles were partly dissolved, Cu (a nonnegligible contribution) was, in addition, present and analyzed in the nourishing medium present beneath the cells. This study presents cellular doses induced by Cu particles and demonstrates difficulties with deposition of nanoparticles at the ALI and of partially soluble particles.
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| 3. |
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| 4. |
- Cronholm, Pontus
(författare)
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Toxicity of metal and metal oxide nanoparticles : the importance of physicochemical properties and cellular uptake
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The use of nanoparticles holds great promises in many technical as well as medical applications. However, development of new technologies, such as nanotechnology, is connected with uncertainties and risks. The same properties that from a technical point of view are beneficial may in other aspects be unwanted and harmful for both humans and the environment. In order to avoid unnecessary risks and facilitate the use of safe nanotechnology there is a need for adequate toxicological research, as well as risk assessments of nanoparticles and nanotechnologies. This thesis is mainly focusing on the hazards (toxicity) of nanoparticles, and more specifically metal and metal oxide containing nanoparticles. In paper I, the ability of different nanoparticles, as well as multi-walled carbon nanotubes (MWCNT), to induce a cellular response based on their material composition, was investigated. A high variation between the different particles to induce cytotoxicity, DNA damage and oxidative DNA lesions was observed, where CuO nanoparticles were the most potent. In paper II and III, the role of particle-size on cytotoxicity, DNA damage, mitochondrial depolarization and induction of oxidative DNA lesions was studied. Amongst a number of particle types, only Cu and CuO particles displayed clear size- dependent effects where the nanoparticles were more toxic than the micro-sized particles. In paper IV, the impact of different methodological settings, such as sonication and the use of serum in the cell medium when preparing nanoparticle suspensions, was investigated. Observations revealed that sonication of Cu nanoparticles caused decreased cell viability and increased Cu release compared to non-sonicated particles. Furthermore, serum in the cell medium resulted in less particle agglomeration and increased Cu release compared with medium without serum, but no clear difference in toxicity was detected. In paper III, IV and V, the degree of metal release from Cu, CuO and Ag nanoparticles and subsequent impact on particle toxicity, was investigated. Even though a high Cu release was observed within hours after suspending the particles in cell medium, a toxic response was dependent on intracellular particle uptake, via a so-called Trojan horse type mechanism. In comparison to the high toxicity observed for Cu and CuO nanoparticles, no DNA damage or cytotoxicity was observed after exposure to the Ag nanoparticles, which is likely to depend on low Ag release from the particles. In conclusion, a key property of metal and metal oxide nanoparticles is the release of ions facilitating a toxicological response. Via a so-called Trojan horse type mechanism the solid particles can facilitate uptake into cells and subsequently release toxic ionic 
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| 5. |
- Cronholm, Pontus, et al.
(författare)
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Effect of sonication and serum proteins on copper release from copper nanoparticles and the toxicity towards lung epithelial cells
- 2011
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Ingår i: Nanotoxicology. - : Informa UK Limited. - 1743-5390 .- 1743-5404. ; 5:2, s. 269-281
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Tidskriftsartikel (refereegranskat)abstract
- Different methodological settings can influence particle characteristics and toxicity in nanotoxicology. The aim of this study was to investigate how serum proteins and sonication of Cu nanoparticle suspensions influence the properties of the nanoparticles and toxicological responses on human lung epithelial cells. This was investigated by using methods for particle characterization (photon correlation spectroscopy and TEM) and Cu release (atomic absorption spectroscopy) in combination with assays for analyzing cell toxicity (MTT-, trypan blue- and Comet assay). The results showed that sonication of Cu nanoparticles caused decreased cell viability and increased Cu release compared to non-sonicated particles. Furthermore, serum in the cell medium resulted in less particle agglomeration and increased Cu release compared with medium without serum, but no clear difference in toxicity was detected. Few cells showed intracellular Cu nanoparticles due to fast release/dissolution processes of Cu. In conclusion; sonication can affect the toxicity of nanoparticles.
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| 6. |
- Midander, Klara, et al.
(författare)
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Surface characteristics, copper release, and toxicity of nano- and micrometer-sized copper and copper(II) oxide particles : a cross-disciplinary study.
- 2009
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Ingår i: Small (Weinheim an der Bergstrasse, Germany). - : Wiley. - 1613-6829 .- 1613-6810. ; 5:3, s. 389-99
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Tidskriftsartikel (refereegranskat)abstract
- An interdisciplinary and multianalytical research effort is undertaken to assess the toxic aspects of thoroughly characterized nano- and micrometer-sized particles of oxidized metallic copper and copper(II) oxide in contact with cultivated lung cells, as well as copper release in relevant media. All particles, except micrometer-sized Cu, release more copper in serum-containing cell medium (supplemented Dulbecco's minimal essential medium) compared to identical exposures in phosphate-buffered saline. Sonication of particles for dispersion prior to exposure has a large effect on the initial copper release from Cu nanoparticles. A clear size-dependent effect is observed from both a copper release and a toxicity perspective. In agreement with greater released amounts of copper per quantity of particles from the nanometer-sized particles compared to the micrometer-sized particles, the nanometer particles cause a higher degree of DNA damage (single-strand breaks) and cause a significantly higher percentage of cell death compared to cytotoxicity induced by micrometer-sized particles. Cytotoxic effects related to the released copper fraction are found to be significantly lower than the effects related to particles. No DNA damage is induced by the released copper fraction.
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