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

TY - JOUR

T1 - The intracellular number of magnetic nanoparticles modulates the apoptotic death pathway after magnetic hyperthermia treatment

AU - Beola, Lilianne

AU - Asín, Laura

AU - Roma-Rodrigues, Catarina

AU - Fernandez-Afonso, Yilian

AU - Fratila, Raluca M.

AU - Serantes, David

AU - Ruta, Sergiu

AU - Chantrell, Roy W.

AU - Fernandes, Alexandra R.

AU - Baptista, Pedro V.

AU - de la Fuente, Jesus M.

AU - Grazu, Valeria

AU - Gutierrez, Lucía

N1 - © 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.

PY - 2020/9/30

Y1 - 2020/9/30

N2 - 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.

AB - 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.

KW - 3D cell culture

KW - Apoptosis

KW - Cell death pathways

KW - Iron oxides

KW - Macrophages

KW - Magnetic hyperthermia

KW - Nanoparticle uptake

UR - http://www.scopus.com/inward/record.url?scp=85092681039&partnerID=8YFLogxK

U2 - 10.1021/acsami.0c12900

DO - 10.1021/acsami.0c12900

M3 - Article

C2 - 32870658

AN - SCOPUS:85092681039

SN - 1944-8244

VL - 12

SP - 43474

EP - 43487

JO - ACS applied materials & interfaces

JF - ACS applied materials & interfaces

IS - 39

ER -