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 - PCIN-2017-060
FCT/MCTES M-ERA NET/2/0008/2016
PGC2018-096016-B-I00
BIO2017-84246-C2-1-R
UIDB/04378/2020
ED431E2018/08
EP/K031589/1
CAS18/00233
RYC-2014-15512
RYC-2015-17640
Sem PDF conforme despacho.
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 -