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A Novel Nanosafety Approach Using Cell Painting, Metabolomics, and Lipidomics Captures the Cellular and Molecular Phenotypes Induced by the Unintentionally Formed Metal-Based (Nano)Particles
Örebro University, School of Science and Technology. Inflammatory Response and Infection Susceptibility Centre (iRiSC), Faculty of Medicine and Health, Örebro University, Örebro, Sweden. (Man-Technology-Environment Research Center (MTM))ORCID iD: 0000-0002-2403-7989
Örebro University, School of Science and Technology. (Man-Technology-Environment Research Center (MTM))ORCID iD: 0000-0001-9713-2365
Örebro University, School of Science and Technology. (Man-Technology-Environment Research Center (MTM); Centre for Applied Autonomous Sensor Systems (AASS), Mobile Robotics and Olfaction Lab (MRO))ORCID iD: 0000-0002-2744-0132
Örebro University, School of Science and Technology.ORCID iD: 0000-0002-8144-8821
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2023 (English)In: Cells, E-ISSN 2073-4409, Vol. 12, no 2, article id 281Article in journal (Refereed) Published
Abstract [en]

Additive manufacturing (AM) or industrial 3D printing uses cutting-edge technologies and materials to produce a variety of complex products. However, the effects of the unintentionally emitted AM (nano)particles (AMPs) on human cells following inhalation, require further investigations. The physicochemical characterization of the AMPs, extracted from the filter of a Laser Powder Bed Fusion (L-PBF) 3D printer of iron-based materials, disclosed their complexity, in terms of size, shape, and chemistry. Cell Painting, a high-content screening (HCS) assay, was used to detect the subtle morphological changes elicited by the AMPs at the single cell resolution. The profiling of the cell morphological phenotypes, disclosed prominent concentration-dependent effects on the cytoskeleton, mitochondria, and the membranous structures of the cell. Furthermore, lipidomics confirmed that the AMPs induced the extensive membrane remodeling in the lung epithelial and macrophage co-culture cell model. To further elucidate the biological mechanisms of action, the targeted metabolomics unveiled several inflammation-related metabolites regulating the cell response to the AMP exposure. Overall, the AMP exposure led to the internalization, oxidative stress, cytoskeleton disruption, mitochondrial activation, membrane remodeling, and metabolic reprogramming of the lung epithelial cells and macrophages. We propose the approach of integrating Cell Painting with metabolomics and lipidomics, as an advanced nanosafety methodology, increasing the ability to capture the cellular and molecular phenotypes and the relevant biological mechanisms to the (nano)particle exposure.

Place, publisher, year, edition, pages
MDPI, 2023. Vol. 12, no 2, article id 281
Keywords [en]
Additive manufacturing, high-content screening (HCS), inflammation, multivariate analysis, nanoparticle emissions, new approach methodologies (NAMs), targeted metabolomics
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:oru:diva-103319DOI: 10.3390/cells12020281ISI: 000916977400001PubMedID: 36672217Scopus ID: 2-s2.0-85146736511OAI: oai:DiVA.org:oru-103319DiVA, id: diva2:1729889
Note

Funding agency:

General Electric 20190107 20160019

Available from: 2023-01-23 Created: 2023-01-23 Last updated: 2024-03-05Bibliographically approved

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Alijagic, AndiScherbak, NikolaiKotlyar, OleksandrKarlsson, PatrikAmiryousefi, AliAndersson, LenaLarsson, MariaHedbrant, AlexanderSalihovic, SamiraHyötyläinen, TuuliaRepsilber, DirkSärndahl, EvaEngwall, Magnus

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Alijagic, AndiScherbak, NikolaiKotlyar, OleksandrKarlsson, PatrikAmiryousefi, AliAndersson, LenaPersson, AlexanderLarsson, MariaHedbrant, AlexanderSalihovic, SamiraHyötyläinen, TuuliaRepsilber, DirkSärndahl, EvaEngwall, Magnus
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