Interplay of cell death signaling pathways mediated by alternating magnetic field gradient

The ability to control or manipulate the pathways leading to cell death plays a pivotal role in cancer treatment. We demonstrate magneto-actuation of magnetic nanoparticles (MNPs) to induce different cell death signaling pathways, exemplifying the intricate interplay between apoptosis and necrosis. In vitro cell experiments show the cell viabilities decreases with increasing field strength and is lower in cells treated with low aspect ratio MNPs. In a strong vertical magnetic field gradient, the MNPs were able to apply sufficient force on the cell to trigger the intracellular pathway for cell apoptosis, thus significantly reducing the cell viability. The quantification of apoptotic and necrotic cell populations by fluorescence dual staining attributed the cell death mechanism to be predominantly apoptosis in a magnetic field gradient. In contrast, the MNPs in an alternating magnetic field gradient can effectively rupture the cell membrane leading to higher lactate dehydrogenase leakage and lower cell viability, proving to be an effective induction of cell death via necrosis.