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In this work, the capability of primary, monocyte-derived dendritic cells(DCs) to uptake iron oxide magnetic nanoparticles (MNPs) is assessed and astrategy to induce selective cell death in these MNP-loaded DCs using externalalternating magnetic fields (AMFs) is reported. No significant decrease in thecell viability of MNP-loaded DCs, compared to the control samples, was observedafter five days of culture. The amount of MNPs incorporated into the cytoplasmwas measured by magnetometry, which confirmed that 1 to 5 pg of the particleswere uploaded per cell. The intracellular distribution of these MNPs, assessedby transmission electron microscopy, was found to be primarily inside theendosomic structures. These cells were then subjected to an AMF for 30 min, andthe viability of the blank DCs (i.e., without MNPs), which were used as controlsamples, remained essentially unaffected. However, a remarkable decrease ofviability from approximately 90% to 2-5% of DCs previously loaded with MNPs wasobserved after the same 30 min exposure to an AMF. The same results wereobtained using MNPs having either positive (NH2+) or negative (COOH-) surfacefunctional groups. In spite of the massive cell death induced by application ofAMF to MNP-loaded DCs, the amount of incorporated magnetic particles did notraise the temperature of the cell culture. Clear morphological changes at thecell structure after magnetic field application were observed using scanningelectron microscopy. Therefore, local damage produced by the MNPs could be themain mechanism for the selective cell death of MNP-loaded DCs under an AMF.Based on the ability of these cells to evade the reticuloendothelial system,these complexes combined with an AMF should be considered as a potentiallypowerful tool for tumour therapy.

Cell death induced by the application of alternating magnetic fields to nanoparticle-loaded dendritic cells