Cell Behavioral Changes after the Application of Magneto-Mechanical Activation to Normal and Cancer Cells

Abstract

In vitro cell exposure to nanoparticles, depending on the applied concentration, can help in the development of theranostic tools to better detect and treat human diseases. Recent studies have attempted to understand and exploit the impact of magnetic field-actuated internalized magnetic nanoparticles (MNPs) on the behavior of cancer cells. In this work, the viability rate of MNP’s-manipulated cancerous (MCF-7, MDA-MB-231) and non-cancerous (MCF-10A) cells was investigated in three different types of low-frequency magnetic fields: static, pulsed, and rotating field mode. In the non-cancerous cell line, the cell viability decreased mostly in cells with internalized MNPs and those treated with the pulsed field mode. In both cancer cell lines, the pulsed field mode was again the optimum magnetic field, which together with internalized MNPs caused a large decrease in cells’ viability (50–55% and 70% in MCF-7 and MDA-MB-231, respectively) while the static and rotating field modes maintained the viability at high levels. Finally, F-actin staining was used to observe the changes in the cytoskeleton and DAPI staining was performed to reveal the apoptotic alterations in cells’ nuclei before and after magneto-mechanical activation. Subsequently, reduced cell viability led to a loss of actin stress fibers and apoptotic nuclear changes in cancer cells subjected to MNPs triggered by a pulsed magnetic field.

Synergistic Effect of Combined Treatment with Magnetic Hyperthermia and Magneto-Mechanical Stress of Breast Cancer Cells

“…Their iron oxide core is covered with a hydrophilic polymer matrix (starch) to protect them against aggregation by foreign ions. All consumables used for cell cultivation have been described previously [18]. Transmission electron microscopy (TEM) and vibrating-sample magnetometer (VSM) measurements of these commercial MNPs have already been published [19,23], confirming the spherical shape of the MNPs, while hysteresis loops at low (5 K) and high temperature (300 K) yielded a distinct saturation magnetization M s (5K) = 50 and Ms (300K) = 40 Am 2 /kg.…”

“…In our previous study, we established that pulsed filed mode in presence of MNPs (Pulsed (+) MNPs) of MM activation caused the highest cytotoxic effect on breast cancer cells [18]. For that purpose, in the present study, we used that mode of MM activation in combination with MHT in order to check, if the combined treatment can induce an enhanced cytotoxic effect on breast cancer cells.…”

“…This result is important because it shows that the MNPs themselves do not cause a toxic effect on the cells. In our previous work, we showed that MNPs at the same initial loading concentration of 100 µg/mL were successfully internalized into cancer cells [18], and after 24 h of incubation they reached a concentration of 22,891 MNPs/cell, which proved to be toxic to cancer cells, when applying a low-frequency magnetic field [18]. The treatment of cancer cells (MCF-7) with MM (Pulsed (+) MNPs) revealed a long time (after 120 h incubation) effect on cell viability (under 50% decrease, as seen in Figure 2).…”

“…In addition, when MNPs are internalized in the presence of an alternating magnetic field, they can cause mechanical disruption of lysosomes, the release of lysosomal contents, and finally cell death [16,17]. In our previous studies, we showed that application a magneto-mechanical stress (especially pulsed field mode) in combination with MNPs caused the internalization of MNPs, decreased viability, and actin stress fiber alterations and apoptotic changes in MCF-7 and MDA-MB-231 cancer cell lines [18,19].…”

Magnetomechanical Stress-Induced Colon Cancer Cell Growth Inhibition

“…LMP, a process that leads to the release of the hydrolases from the lysosomal lumen to the cytosol, has been under investigation as a novel therapeutic strategy and proven effective in many cancer models [55]. Specifically, magnetomechanical disruption of the lysosomal membrane via the actuation of internalized MNPs has been successfully achieved in vitro [56][57][58][59][60][61]. The force generated here via the magnetic actuation of the internalized MNPs was calculated to reach ≈29 pN per cell.…”