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Development and comparison of in vitro toxicity methods for nanoparticles: Focus on lung cell exposure
Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.ORCID iD: 0000-0003-1092-7064
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Concerns for the toxic effects of airborne nanoparticles have been raised along with the increasing production of nanostructured materials. However, the health risks of nanoparticle exposure are currently not fully understood. The most commonly used techniques to study nanoparticle toxicity, both in vivo and in vitro, have several limitations. These include for example challenges regarding dosimetry or the lack of similarity of overall exposure conditions and the physico-chemical particle characteristics. Therefore, there is a need for more advanced methods to study the pulmonary toxicity of airborne nanoparticles.

This thesis presents the use of air-liquid interface (ALI) systems as a possible approach to this challenge. While utilizing the direct deposition of airborne nanoparticles on lung cell cultures, the ALI approach can more realistically mimic the characteristics of the human respiratory tract and the interactions of airborne particles with lung cells. This allows for a better understanding of the health risks posed by inhalation exposure to nanoparticles.

Two different ALI systems were investigated and their use was compared to submerged exposure methods. One of the ALI exposure systems utilizes electrostatic force in order to make the deposition of charged airborne nanoparticles more efficient, while the other system operates by the diffusion of airborne nanoparticles. ALI and submerged exposure methods were used for investigating the cytotoxicity and genotoxicity of Ni-containing nanoparticles as well as the cytotoxicity and inflammatory potential of CeO2-nanoparticles. While Ag-nanoparticles were used as a test material during the development of the electrostatic ALI system, their cytotoxicity was investigated in ALI exposure. In conclusion, the ALI exposure methods provide more realistic conditions and make the particle dosimetry more controllable.

Place, publisher, year, edition, pages
Stockholm: Department of Environmental Science and Analytical Chemistry, Stockholm University , 2016. , 40 p.
National Category
Environmental Sciences
Research subject
Applied Environmental Science
Identifiers
URN: urn:nbn:se:su:diva-134125ISBN: 978-91-7649-490-5OAI: oai:DiVA.org:su-134125DiVA: diva2:1033173
Public defence
2016-11-25, William-Olssonsalen, Geovetenskapens hus, Svante Arrhenius väg 14, Stockholm, 10:00 (English)
Opponent
Supervisors
Note

At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 3: Manuscript. Paper 4: Manuscript.

 

Available from: 2016-11-01 Created: 2016-10-02 Last updated: 2016-10-24Bibliographically approved
List of papers
1. Nickel release, ROS generation and toxicity of Ni and NiO micro- and nanoparticles
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2016 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 7, e0159684Article in journal (Refereed) Published
Abstract [en]

Occupational exposure to airborne nickel is associated with an elevated risk for respiratory tract diseases including lung cancer. Therefore, the increased production of Ni-containing nanoparticles necessitates a thorough assessment of their physical, chemical, as well as toxicological properties. The aim of this study was to investigate and compare the characteristics of nickel metal (Ni) and nickel oxide (NiO) particles with a focus on Ni release, reactive oxygen species (ROS) generation, cellular uptake, cytotoxicity and genotoxicity. Four Ni-containing particles of both nano-size (Ni-n and NiO-n) and micron-size (Ni-m1 and Ni-m2) were tested. The released amount of Ni in solution was notably higher in artificial lysosomal fluid (e.g. 80–100 wt% for metallic Ni) than in cell medium after 24h (ca. 1–3 wt% for all particles). Each of the particles was taken up by the cells within 4 h and they remained in the cells to a high extent after 24 h post-incubation. Thus, the high dissolution in ALF appeared not to reflect the particle dissolution in the cells. Ni-m1 showed the most pronounced effect on cell viability after 48 h (alamar blue assay) whereas all particles showed increased cytotoxicity in the highest doses (20–40 μg cm2) when assessed by colony forming efficiency (CFE). Interestingly an increased CFE, suggesting higher proliferation, was observed for all particles in low doses (0.1 or 1 μg cm-2). Ni-m1 and NiO-n were the most potent in causing acellular ROS and DNA damage. However, no intracellular ROS was detected for any of the particles. Taken together, micron-sized Ni (Ni-m1) was more reactive and toxic compared to the nano-sized Ni. Furthermore, this study underlines that the low dose effect in terms of increased proliferation observed for all particles should be further investigated in future studies.

National Category
Environmental Sciences
Research subject
Applied Environmental Science
Identifiers
urn:nbn:se:su:diva-134001 (URN)10.1371/journal.pone.0159684 (DOI)000380169600081 ()
Available from: 2016-09-26 Created: 2016-09-26 Last updated: 2016-10-06Bibliographically approved
2. Optimization of an air–liquid interface exposure system for assessing toxicity of airborne nanoparticles
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2016 (English)In: Journal of Applied Toxicology, ISSN 0260-437X, E-ISSN 1099-1263, Vol. 36, no 10, 1294-1301 p.Article in journal (Refereed) Published
Abstract [en]

The use of refined toxicological methods is currently needed for characterizing the risks of airborne nanoparticles (NPs) to human health. To mimic pulmonary exposure, we have developed an air–liquid interface (ALI) exposure system for direct deposition of airborne NPs on to lung cell cultures. Compared to traditional submerged systems, this allows more realistic exposure conditions for characterizing toxicological effects induced by airborne NPs. The purpose of this study was to investigate how the deposition of silver NPs (AgNPs) is affected by different conditions of the ALI system. Additionally, the viability and metabolic activity of A549 cells was studied following AgNP exposure. Particle deposition increased markedly with increasing aerosol flow rate and electrostatic field strength. The highest amount of deposited particles (2.2 μg cm–2) at cell-free conditions following 2 h exposure was observed for the highest flow rate (390 ml min–1) and the strongest electrostatic field (±2 kV). This was estimated corresponding to deposition efficiency of 94%. Cell viability was not affected after 2 h exposure to clean air in the ALI system. Cells exposed to AgNPs (0.45 and 0.74 μg cm–2) showed significantly (P < 0.05) reduced metabolic activities (64 and 46%, respectively). Our study shows that the ALI exposure system can be used for generating conditions that were more realistic for in vitro exposures, which enables improved mechanistic and toxicological studies of NPs in contact with human lung cells.

Keyword
ALI, nanotoxicology, in vitro, silver, nanoparticles, electrostatic, A549
National Category
Environmental Sciences
Research subject
Applied Environmental Science
Identifiers
urn:nbn:se:su:diva-134002 (URN)10.1002/jat.3304 (DOI)000382699000006 ()
Available from: 2016-09-26 Created: 2016-09-26 Last updated: 2016-10-06Bibliographically approved
3. In vitro genotoxicity assessment of airborne nickel nanoparticles using air-liquid interface exposure
Open this publication in new window or tab >>In vitro genotoxicity assessment of airborne nickel nanoparticles using air-liquid interface exposure
2016 (English)Manuscript (preprint) (Other academic)
National Category
Environmental Sciences
Research subject
Applied Environmental Science
Identifiers
urn:nbn:se:su:diva-134006 (URN)
Available from: 2016-09-26 Created: 2016-09-26 Last updated: 2016-10-06Bibliographically approved
4. Dry generation of CeO2 nanoparticles and deposition onto a co-culture of A549 and THP-1 cells in air-liquid interface – dosimetry consideration and comparison to submerged exposure
Open this publication in new window or tab >>Dry generation of CeO2 nanoparticles and deposition onto a co-culture of A549 and THP-1 cells in air-liquid interface – dosimetry consideration and comparison to submerged exposure
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(English)Manuscript (preprint) (Other academic)
National Category
Environmental Sciences
Research subject
Applied Environmental Science
Identifiers
urn:nbn:se:su:diva-134007 (URN)
Available from: 2016-09-26 Created: 2016-09-26 Last updated: 2016-10-06Bibliographically approved

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