Magnetomechanical Stress-Induced Colon Cancer Cell Growth Inhibition

Abstract

The application of magnetomechanical stress in cells using internalized magnetic nanoparticles (MNPs) actuated by low-frequency magnetic fields has been attracting considerable interest in the field of cancer research. Recent developments prove that magnetomechanical stress can inhibit cancer cells’ growth. However, the MNPs’ type and the magnetic field’s characteristics are crucial parameters. Their variability allows multiple combinations, which induce specific biological effects. We previously reported the antiproliferative effects induced in HT29 colon cancer cells by static-magnetic-field (200 mT)-actuated spherical MNPs (100 nm). Herein, we show that similar growth inhibitory effects are induced in other colon cancer cell lines. The effect of magnetomechanical stress was also examined in the growth rate of tumor spheroids. Moreover, we examined the biological mechanisms involved in the observed cell growth inhibition. Under the experimental conditions employed, no cell death was detected by PI (propidium iodide) staining analysis. Flow cytometry and Western blotting revealed that G2/M cell cycle arrest might mediate the antiproliferative effects. Furthermore, MNPs were found to locate in the lysosomes, and a decreased number of lysosomes was detected in cells that had undergone magnetomechanical stress, implying that the mechanical activation of the internalized MNPs could induce lysosome membrane disruption. Of note, the lysosomal acidic conditions were proven to affect the MNPs’ magnetic properties, evidenced by vibrating sample magnetometry (VSM) analysis. Further research on the combination of the described magnetomechanical stress with lysosome-targeting chemotherapeutic drugs could lay the groundwork for the development of novel anticancer combination treatment schemes.