Necrosis-Dominated Killing of Melanoma Cells by Microsecond Pulsed Magnetic Fields and Iron Oxide Nanoparticles via Cytoskeletal and Membrane Damage

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Abstract
Magnetomechanical therapy (MMT), an emerging and promising physical modality for cancer treatment, holds significant potential in oncology. Nevertheless, the precise mechanisms underlying its cytotoxic effects and the specific cellular targets involved, particularly in the context of pulsed magnetic fields (PMFs), remain incompletely understood. In this study, we investigated the therapeutic efficacy of microsecond pulsed magnetic fields (μs-PMFs) combined with iron oxide nanoparticles (IONPs) in A375 melanoma cells. Cell apoptosis and necrosis were quantified using YO-PRO-1/propidium iodide (PI) double staining to evaluate both treatment effectiveness and the predominant mode of cell death. In addition, fluorescent labeling of the cytoskeleton, cell membrane, and lysosomes with specific fluorophores was performed to identify the primary cellular structures affected by magnetic forces during treatment. The results demonstrated that MMT significantly reduced A375 cell viability, achieving an overall cell death rate of 61.16%. Notably, necrosis was identified as the predominant mode of cell death, accounting for 52.38% of total cell mortality. Furthermore, the cell membrane, cytoskeleton, and lysosomes were determined to be major cellular targets of magnetomechanical disruption. These findings provide critical insights into the cellular mechanisms of μs-PMF induced MMT and support its continued development toward clinical translation as a novel anti-tumor strategy.
Funding Information
  • National Natural Science Foundation of China (52077022)
  • National Natural Science Foundation of China (BP0820005)

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