The Cytotoxicity of Metal Nanoparticles Depends on Their Synergistic Interactions |
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Authors: | Barbara Korzeniowska Micaella P. Fonseca Vladimir Gorshkov Lilian Skytte Kaare L. Rasmussen Henrik D. Schrøder Frank Kjeldsen |
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Affiliation: | 1. Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, Odense, M 5230 Denmark;2. Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, Odense, M 5230 Denmark;3. Department of Pathology, Odense University Hospital, University of Southern Denmark, J.B. Winsløws Vej 15, Odense, C 5000 Denmark |
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Abstract: | With a steady growth in use of engineered nanoparticles (NPs) in consumer products the unintended exposure to humans has increased. The risks associated with introduction of NPs in the environment have been widely investigated, but mostly for single type of NPs. Herein, a single NP and NP co-exposure study is reported: the cellular effects of silver and platinum NPs on the main components of the blood–brain barrier, human cerebral microvascular endothelial cells, and human primary astrocytes. The synergy is quantitatively evaluated as per the Chou–Talalay method. NP co-exposure synergistically inhibits proliferation of both cell types, to a greater extent for endothelial cells. In addition, astrocytes are more tolerant to NPs. The mechanism of synergy with short-duration incubation time points (up to 30 min) is further explored. Although intracellular trafficking studies and quantitative assessments of NP uptake does not explain the mechanisms of synergistic cytotoxicity, a proteomics analysis suggests that it arises from activation of an immune modulating response and deregulation of the extracellular matrix organization. The substantial synergetic effects in the co-exposure studies highlight the importance of this work in relation to assessment of the health risks associated with nanomaterials. |
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Keywords: | blood–brain barrier cytotoxicity mass spectrometry metal nanoparticles synergy effects |
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