Controlled Cell Death by Magnetic Hyperthermia: Effects of Exposure Time, Field Amplitude, and Nanoparticle Concentration
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To investigate the effects of alternating magnetic fields (AMF) on the death rate of dendritic cells (DCs) loaded with magnetic nanoparticles (MNPs) as heating agents. AMF exposure time and amplitude as well as the MNPs concentration were screened to assess the best conditions for a controlled field-induced cell death.
Human-monocyte-derived DCs were co-incubated with dextran-coated MNPs. The cells were exposed to AMF (f = 260 kHz; 0 < H0 < 12.7 kA/m) for intervals from 5 to 15 min. Morphology changes were assessed by scanning electron microscopy. Cell viability was measured by Trypan blue and fluorescence-activated cell sorting (FACS) using Annexin-propidium iodide markers.
We were able to control the DCs viability by a proper choice AMF amplitude and exposure time, depending on the amount of MNPs uploaded. About 20% of cells showed Annexin-negative/PI-positive staining after 5–10 min of AMF exposure.
Controlled cell death of MNP-loaded DCs can be obtained by adequate tuning of the physical AMF parameters and MNPs concentration. Necrotic-like populations were observed after exposure times as short as 10 min, suggesting a fast underlying mechanism for cell death. Power absorption by the MNPs might locally disrupt endosomic membranes, thus provoking irreversible cell damage.
KEY WORDSalternating magnetic fields cell death dendritic cells magnetic hyperthermia magnetic nanoparticles
Acknowledgments & Disclosures
This work was supported by the Spanish Ministerio de Ciencia e Innovación (project MICINN MAT2010-19326 and CONSOLIDER NANOBIOMED CS-27 2006) and IBERCAJA. LA acknowledges MICINN by financial support through a FPU fellowship. The University of Zaragoza, along with their researchers, have filled patents related to the technology and intellectual property reported here. G.F.G. and M.R. I. have equity in nB Nanoscale Biomagnetics S.L. The other authors declare that they do not have any affiliations that would lead to conflict of interest. We are grateful to the I + CS staff (University Hospital, Zaragoza) Dr. J. Godino (FACS experiments) and Dr. M. Royo Cañas (confocal microscopy) for their advice and technical support.
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