Beola, Lilianne, Asín, Laura, Roma-Rodrigues, Catarina et al. (10 more authors) (2020) The intracellular number of magnetic nanoparticles modulates the apoptotic death pathway after magnetic hyperthermia treatment. ACS Applied Materials and Interfaces. pp. 43474-43487. ISSN 1944-8252
Abstract
Magnetic hyperthermia is a cancer treatment based on the exposure of magnetic nanoparticles to an alternating magnetic field in order to generate local heat. In this work, 3D cell culture models were prepared to observe the effect that a different number of internalized particles had on the mechanisms of cell death triggered upon the magnetic hyperthermia treatment. Macrophages were selected by their high capacity to uptake nanoparticles. Intracellular nanoparticle concentrations up to 7.5 pg Fe/cell were measured both by elemental analysis and magnetic characterization techniques. Cell viability after the magnetic hyperthermia treatment was decreased to <25% for intracellular iron contents above 1 pg per cell. Theoretical calculations of the intracellular thermal effects that occurred during the alternating magnetic field application indicated a very low increase in the global cell temperature. Different apoptotic routes were triggered depending on the number of internalized particles. At low intracellular magnetic nanoparticle amounts (below 1 pg Fe/cell), the intrinsic route was the main mechanism to induce apoptosis, as observed by the high Bax/Bcl-2 mRNA ratio and low caspase-8 activity. In contrast, at higher concentrations of internalized magnetic nanoparticles (1−7.5 pg Fe/cell), the extrinsic route was observed through the increased activity of caspase-8. Nevertheless, both mechanisms may coexist at intermediate iron concentrations. Knowledge on the different mechanisms of cell death triggered after the magnetic hyperthermia treatment is fundamental to understand the biological events activated by this procedure and their role in its effectiveness.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2020 American Chemical Society. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details. |
Keywords: | 3D cell culture,Apoptosis,Cell death pathways,Iron oxides,Macrophages,Magnetic hyperthermia,Nanoparticle uptake |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > York Institute for Materials Research The University of York > Faculty of Sciences (York) > Physics (York) |
Depositing User: | Pure (York) |
Date Deposited: | 20 Nov 2020 17:40 |
Last Modified: | 16 Oct 2024 17:08 |
Published Version: | https://doi.org/10.1021/acsami.0c12900 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1021/acsami.0c12900 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:168240 |
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Filename: Manuscript_Beola_final_1_.pdf
Description: Manuscript Beola-final (1)