Magnetic hyperthermia (MH) is a nanotechnology-driven therapy that seizes the heat release of magnetic nanoparticles when exposed to an alternating magnetic field. It has already been and is currently trialed in clinical settings as adjuvant of chemotherapy and radiotherapy to successfully treat several types of tumors [1, 2]. In silico testing (computer simulations) allows us to mimic several clinical situations and to evaluate the treatment safety in terms of dosimetry and temperature rise, including possible hot spots due to eddy currents, in a cheap and fast way. MH has taken advantages of this virtual testing in its way towards personalized therapy. The versatility of the simulations to evaluate many clinical setups allows us to study the actual risks of the current exclusion criteria [1, 3]. Nowadays, bearing any kind of metallic object, orthopedic implants for example, constitutes a contraindication for the treatment. This is based on the knowledge obtained from MRI related studies, but there is an important lack in the literature about the quantification of these risks in the context of clinical MH. In this work, we use computer simulations to study the actual risks of potential MH patients carrying different orthopedic prosthesis, as well as the influence of the presence of this metallic object in the effective magnetic field reaching the nanoparticles site. We have considered different treatment setups varying tumor locations, implant types and materials to evaluate the temperature increase and the dosimetric values in the major tissue groups. These safety parameters have been included in a multi-criteria decision analysis to asses a risk index for each tissue group in every clinical situation analyzed [4]. Acknowledgements We acknowledge COST Action MyWave (CA 17115), NoCanTher project (grant agreement No 685795), Regional Government of Madrid under contract PEJD-2017-PRE/IND-3663, Spanish Ministry of Economy and Competitiveness through the grants MAT2017-85617-R, Ramón y Cajal RYC2018-025253-I, the “Severo Ochoa” Program for Centers of Excellence in R&D (SEV-2016-0686) and the support of NVIDIA Corporation through the GPU Grant Program with the donation of the Quadro P6000 GPU used in this work.

![](https://assets.underline.io/uploads/markdown_image/1/image/5b88302d4b166afa56c0e9833b44c1ec.jpg)

In Silico Safety Analysis of Magnetic Hyperthermia Treatments of Implant-Bearing Patients

Achieving homogeneous tumour heating is one of the most long-standing challenges in magnetic hyperthermia for cancer therapy. Clinical studies must meet strict safety regulations that require knowledge and control over the physical properties of the chosen magnetic nanoparticles [1]. Whereas it is well-established that the heat released by magnetic nanostructures is influenced by interparticle interactions, as of today there is no method to analyze heat exchange at single-particle level in interacting systems at nonzero temperature. This gap needs to be bridged so to harness nanoparticle magnetization dynamics for the sake of biomedical applications. Building on previous theoretical work [2], we present an equation to estimate the heat dissipation of individual, interacting particles at nonzero temperature that perform both field-induced and thermal switching. After validating this equation, we use the macrospin simulation tool Vinamax [3], to investigate a system of interacting particles with different anisotropies, as we showed in this contribution [4]. Our preliminary results indicate (see figure) that the generated heat becomes more homogeneously distributed at larger fields. We believe that this homogenization of the particle heating will help to achieve a more homogenized heating of tumors during hyperthermia treatments. The use of the proposed equation would simplify the selection process of optimum nanoparticle distributions leading to optimal tumour heating. Its simplicity and flexibility also allow it to be integrated into multi-scale, multi-physics simulations to accurately assess the magnetic hyperthermia therapy without impacting the overall computational time.

![](https://assets.underline.io/uploads/markdown_image/1/image/cd66b63a757f78697365ef1ca41b5bd1.jpg)

Figure: Heat generated in a system consisting of two interacting nanoparticles with different anisotropies. Both particles show switching behavior as soon as the excitation field amplitude overcomes their anisotropy barrier. The heat generation tends to become more uniform with increasing excitation fields.

Homogenization of Heating in Magnetic Hyperthermia Through Exploitation of Magnetisation Dynamics of Interacting Particles

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

We describe two accessible and successful microfluidic strategies to expose human pluripotent stem cells to spatial gradients of differentiation-inducing extracellular signals in vitro. In addition, coupling with a fluorescent reporter and live-cell imaging allowed us to characterize the spatiotemporal dynamics of differentiation of our spatially patterned cell colonies.

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In Silico Safety Analysis of Magnetic Hyperthermia Treatments of Implant-Bearing Patients

Homogenization of Heating in Magnetic Hyperthermia Through Exploitation of Magnetisation Dynamics of Interacting Particles

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

Spatially controlled stem cell differentiation via morphogen gradients: comparing static and dynamic microfluidic platforms

Hormonal Signaling and Metabolic Tissue Microenvironment in Health and Disease

Adipose Tissue Plasticity in Obesity

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