Transcranial magnetic stimulation (TMS) [1] is a non-invasive pain-free medical technology clinically approved for treatment of drug-resistant depression [2, 3]. TMS uses
pulsed magnetic fields to induce eddy currents [4] in the brain. The biological mechanism of rTMS effects is tought to be mostly relying on the long-lasting changes of the neuronal
excitability and the brain functional plasticity, respoectively [5]. However, the effects of TMS-like fields on non-neuronal cells and artificial systems are almost unknown. The aim of this
study was to explore the potential of repetitive magnetic stimulation (RMS) performed by TMS devices in oncology, controllable drug release and regenerative medicine applications.
Using a standard TMS device “Magstim Rapid2”, we examined effects of >30 experimental regimes of RMS on viability and phenotype of various tumour (glioblastoma, pancreatic, liver,
colorectal [6] and breast cancers) and immune cells (microglia and macrophages). We also tested the effect of RMS on drug release from polymer nanoparticles and reactive oxygen species
generation (ROSG) in cancer and immune cells. Finally, we examined the combined effects of RMS and drugs targeting tissue growth.
RMS selectively modulated viability and functional polarisation of microglia and macrophages in a frequency/intensity-dependent manner and affected the proliferation/viability of cancer
cells (cancer type, frequency- and pulse number-dependent up- and downregulation). RMS induced triggering of drug release from nanoparticles, enhancement of ROSG and additive drug
effects.
Our pioneering findings demonstrate the potential of TMS technology repurposing for immunomodulation, cancer treatment, and drugs and nanomedicines treatment.
We thank Sydney Vital (for seed grant) and Medilink Australia (for providing the “Magstim”). The authors gratefully acknowledge the support of the Macquarie University FMHHS
Laboratory Operations Team. A.G. is thankful for support of her work by the Macquarie University Research Fellowship. 

**References:** 

1. A. T. Barker, R. Jalinous, and I. L. Freeston, "Non-invasive magnetic stimulation of human motor cortex," Lancet, vol. 1, no. 8437, pp. 1106-7, May 11 1985, doi:
10.1016/s0140-6736(85)92413-4. 
2. A. T. Barker, I. L. Freeston, R. Jalinous, and J. A. Jarratt, "Magnetic stimulation of the human brain and peripheral nervous system: an introduction and the results of an initial clinical
evaluation," Neurosurgery, vol. 20, no. 1, pp. 100-9, Jan 1987, doi: 10.1097/00006123-198701000-00024. 
3. P. M. Rossini et al., "Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and peripheral nerves: Basic principles and procedures for routine clinical and
research application. An updated report from an I.F.C.N. Committee," Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology, vol. 126, no.
6, pp. 1071-1107, Jun 2015, doi: 10.1016/j.clinph.2015.02.001. 
4. M. Hallett, "Transcranial magnetic stimulation and the human brain," Nature, vol. 406, no. 6792, pp. 147-50, Jul 13 2000, doi: 10.1038/35018000. 
5. J. P. Lefaucheur et al., "Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS)," (in English), Clinical neurophysiology : official journal
of the International Federation of Clinical Neurophysiology, vol. 125, no. 11, pp. 2150-2206, Nov 2014, doi: 10.1016/j.clinph.2014.05.021. 
6. B. Heng, S. B. Ahn and A. Guller, "TMS-like Magnetic Fields Modulate Metabolic Activity of Hepatic and Colorectal Cancer Cells." IEEE Transactions on Magnetics: 1-1, doi:
10.1109/tmag.2022.3147219.

Beyond conventional neurostimulation: effects of TMS like magnetic fields on cells and nanomaterials and their potential applications in oncology and regenerative medicine

Transcranial magnetic stimulation (TMS)1,2 is clinically used in patients with depression2,3, while the effects of TMS-like magnetic fields on extracranial tissues are almost unknown4. Here, we explored effects of TMS-like repetitive magnetic stimulation (RMS) on metabolic activity of human hepatocellular carcinoma (HCC) and colorectal cancer (CRC) cells. The HuH7 (HCC) and HCT116 (CRC) cell cultures were treated using a TMS device “Magstim Rapid2” with an AFC70 coil. Intermittent RMS (iRMS) modes (4 trains of 150 pulses with frequency f=1, 5, 10, 20 or 40 Hz and equal intertrain intervals) and burst RMS (600 pulses delivered in trains, f=40 Hz/ bursts, f=3 Hz). The coil power output /magnetic field strength was (100% or 50%, B=0.8 T or 0.4 T, respectively) in burst modes or 100% in iRMS. The activity of SDG, an enzyme essential for energy production, was measured by MTT colorimetric assay in 24 h post-RMS. The control groups included: (1) untreated cells, (2) 20 min room temperature control, and (3) strong metabolic suppression by 100% DMSO solution. The main results are shown in Figures 1 and 2. Dashed red lines are CI95% for mean absorbance in the untreated control group; Abs is MTT assay product absorbance, a.u. In HuH7 cells, the tested protocols of RMS either did not change or stimulated the metabolic activity. However, correlation analysis indicated that the modes with higher frequency, burst pattern, and shorter cycles are more probable as suppressors of the liver cancer cells’ metabolism. In HCT116 cells, an iRMS mode 1B100 (f=1 Hz) induced a statistically significant decrease of metabolic activity, while high-frequency iRMS and burst modes stimulated it. In CRC, correlation analysis revealed the opposite to HCC trend of reduction of the metabolic rate at lower frequencies, intermittent PRMS, and the increase of it at high frequencies and burst modes. Our pioneering findings demonstrate the tumour-specific and mode-specific effects of re-purposed TMS technology on hepatic and colorectal cancer cells. The potential of RMS as adjuvant anti-cancer treatment will be discussed. We thank Medilink Australia for providing the “Magstim”.

![](https://assets.underline.io/uploads/markdown_image/1/image/3328edd15f9c1f201697574351fdeb65.jpg)

Figure 1. Effect of RMS on HuH7 cells.

![](https://assets.underline.io/uploads/markdown_image/1/image/181596c78a02d0fe7e97c8ea95446c42.jpg)

Figure 2. Effect of RMS on HCT116 cells.

TMS-like Magnetic Fields Modulate Metabolic Activity of Hepatic and Colorectal Cancer Cells

QOB: Magnetic Stimulation in Biology, Magnetic Fluids and Actuators

technical paper

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**Session chairs:** Yuko Ichiyanagi, Yokohama National University, César de Julian Fernandez, Istituto dei Materiali per l'Elettronica ed il Magnetismo Consiglio Nazionale delle Ricerche and Javier Alonso, Universidad de Cantabria



IOH - Magnetic Biodetection and Therapy I

The 15th Joint MMM-INTERMAG Conference (2022 Joint) is sponsored jointly by AIP Publishing and the IEEE Magnetics Society. Members of the international scientific and engineering communities interested in recent developments in fundamental and applied magnetism are invited to attend and contribute to the technical sessions. The technical program will include invited and contributed papers in oral and poster sessions, invited symposia, a plenary session, and an evening session, with about 1500 presentations overall. This Conference provides an outstanding opportunity for worldwide participants to meet their colleagues and collaborators and discuss developments in all areas of magnetism research.

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Beyond conventional neurostimulation: effects of TMS like magnetic fields on cells and nanomaterials and their potential applications in oncology and regenerative medicine

TMS-like Magnetic Fields Modulate Metabolic Activity of Hepatic and Colorectal Cancer Cells

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