Abstract
Transcranial magnetic stimulation (TMS)1,2 is a widely available technology employing strong ( up to 4 T) pulsed (up to 300 Hz) magnetic fields for diagnostics of brain functions and treatment of various brain disorders. It is currently approved for clinical application in patients with drug-resistant depression2,3, while a spectrum of new indications is emerging5-10. The current paradigm of TMS biological effects implies magnetic induction of Eddy currents in the brain cortical neurons as the leading action mechanism. However, the effects of the TMS-like magnetic fields on non-neuronal cells and some artificial systems is almost unknown. Based on literature analysis4,11-24 and our pilot experimental data, we hypothesize, that the transcranial and extracranial repetitive magnetic stimulation employing pulsed magnetic fields (MFs) generated by TMS devices can have immunomodulatory effects, affect the growth of brain and extracranial malignant tumours and applied in drug delivery control to the cells.This motivated us to explore the effects of designed 18 regimes of patterned repetitive magnetic stimulation (PRMS) on tumor cells of brain (glioblastoma multiforme, GBM) and pancreatic (pancreatic ductal adenocarcinoma) cancers and on microglia (immune cells of the brain). We also tested the effect of PRMS on a drug release from polymer nanoparticles in aqueous environment. A standard TMS device “Magstim Rapid2” with Double 70mm Air Film Coil was applied to the cell cultures spatially configured to correspond to a peak MF of 0.6 T, 0.25-50 Hz frequency, with sessions of 300 or 600 pulses.PRMS selectively modulated the viability and functional polarisation of immune-stimulated microglia in a frequency/intensity-dependent manner (Figure 1) and affected the proliferation/viability of GBM astrocytes and pancreatic cancer cells (frequency- and pulse number-dependent up- and downregulation) (Figure 2). Finally, we show the triggering of the efficient drug release from biocompatible polymer nanoparticles by the 50 Hz/2 min PRMS mode.Our pioneering findings demonstrate the potential of PRMS performed with using of re-purposed TMS equipment for immunomodulation, cancer treatment, brain repair and regeneration.We thank Sydney Vital Translational Cancer Centre (for seed grant) and Medilink Australia (for providing the “Magstim”). **
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