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

Abstract

In this work, the capability of primary, monocyte-derived dendritic cells (DCs) to uptake iron oxide magnetic nanoparticles (MNPs) is assessed and a strategy to induce selective cell death in these MNP-loaded DCs using external alternating magnetic fields (AMFs) is reported. No significant decrease in the cell viability of MNP-loaded DCs, compared to the control samples, was observed after five days of culture. The amount of MNPs incorporated into the cytoplasm was measured by magnetometry, which confirmed that 1 to 5 pg of the particles were uploaded per cell. The intracellular distribution of these MNPs, assessed by transmission electron microscopy, was found to be primarily inside the endosomic structures. These cells were then subjected to an AMF for 30 min, and the viability of the blank DCs (i.e., without MNPs), which were used as control samples, remained essentially unaffected. However, a remarkable decrease of viability from approximately 90% to 2-5% of DCs previously loaded with MNPs was observed after the same 30 min exposure to an AMF. The same results were obtained using MNPs having either positive (NH 2 + ) or negative (COOH -) surface functional groups. In spite of the massive cell death induced by application of AMF to MNP-loaded DCs, the amount of incorporated magnetic particles did not raise the temperature of the cell culture. Clear morphological changes at the cell structure after magnetic field application were observed using scanning electron microscopy. Therefore, local damage produced by the MNPs could be the main 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 potentially powerful tool for tumour therapy.Abbreviations: alternating magnetic field (AMF); dendritic cells (DCs); magnetic nanoparticles (MNPs).

Induced cell toxicity originates dendritic cell death following magnetic hyperthermia treatment

“…However, under AMF, MNP-loaded DCs submitted to an AMF of 260 kHz and 12.7 kA/m and t app of 30 min showed almost 100% cell death in the absence of any increase in temperature. 12 In this study, we sought to understand the mechanism of cell death produced by the application of an electromagnetic field without increases in the temperature of the medium. The uptake of NPs by the DCs was induced by incubation in cell culture medium with increasing concentrations of MNPs.…”

Towards nanomedicines of the future: Remote magneto-mechanical actuation of nanomedicines by alternating magnetic fields

“…For example, the studies involving dendritic cells loaded with small magnetite MNPs (13 nm magnetite core; 10 4 –10 5 MNP/cell) suggested that exposure of the cells to an AMF ( B = 16 mT, f = 260 kHz) results in the death of 95–98% of cells [83,86–88]. At the same time the exposure led to only a marginal increase in the temperature from 26 to 29–30 °C, which could not explain the cytotoxic effect.…”

Targeted Magnetic Nanoparticles for Mechanical Lysis of Tumor Cells by Low-Amplitude Alternating Magnetic Field

“…Here, we used cetuximab coating to target the MNPs specifically to the tumor. The relaxation of MNPs is faster than nonbonding protons and appears as lower MRI signals [21]. Thus, the darker regions in the MRI images clearly demonstrate the presence of the MNPs at the tumor site, indicating the success of cetuximab targeting.…”

“…The four groups of mice were directly exposed to 4 V, 4 Hz unipolar AMFs (as schemed in Figure 1) every other day for 30 min, for a total of 7 treatments over 14 days. Smaller exposure levels have been tolerated well in prior experiments [20,21,22]. All mice were housed in a clean room that did not contain any active magnet source.…”