@article {16134, title = {The Intracellular Number of Magnetic Nanoparticles Modulates the Apoptotic Death Pathway after Magnetic Hyperthermia Treatment}, journal = {ACS Appl Mater Interfaces}, volume = {12}, year = {2020}, note = {

Beola, LilianneAsin, Laura
Roma-Rodrigues, Catarina
Fernandez-Afonso, Yilian
Fratila, Raluca M
Serantes, David
Ruta, Sergiu
Chantrell, Roy W
Fernandes, Alexandra R
Baptista, Pedro V
de la Fuente, Jesus M
Grazu, Valeria
Gutierrez, Lucia
eng
ACS Appl Mater Interfaces. 2020 Sep 30;12(39):43474-43487. doi: 10.1021/acsami.0c12900. Epub 2020 Sep 17.

}, month = {2020}, pages = {43474-43487}, 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.

}, keywords = {3D cell culture, Apoptosis, cell death pathways, iron oxides, Macrophages, Magnetic hyperthermia, nanoparticle uptake}, isbn = {1944-8252 (Electronic)1944-8244 (Linking) }, url = {https://www.ncbi.nlm.nih.gov/pubmed/32870658}, author = {Beola, L. and Asin, L. and Roma-Rodrigues, C. and Fernandez-Afonso, Y. and Fratila, R. M. and Serantes, D. and Ruta, S. and Chantrell, R. W. and Fernandes, A. R. and P.V. Baptista and J.M. de la Fuente and Grazu, V. and Gutierrez, L.} }