The intracellular number of magnetic nanoparticles modulates the apoptotic death pathway after magnetic hyperthermia treatment

Lilianne Beola, Laura Asín, Catarina Roma-Rodrigues, Yilian Fernandez-Afonso, Raluca M. Fratila, David Serantes, Sergiu Ruta, Roy W. Chantrell, Alexandra R. Fernandes, Pedro V. Baptista, Jesus M. de la Fuente, Valeria Grazu, Lucía Gutierrez

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)43474-43487
Number of pages14
JournalACS Applied Materials & Interfaces
Issue number39
Publication statusPublished - 30 Sep 2020


  • 3D cell culture
  • Apoptosis
  • Cell death pathways
  • Iron oxides
  • Macrophages
  • Magnetic hyperthermia
  • Nanoparticle uptake


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