Magnetic and electric response of gold nanoparticles for low frequency applications in biological cells

Abstract

In the context of biomedicine, electromagnetic fields are utilized in a variety of applications, such as cellular reprogramming. At frequencies below the microwave spectrum, electric and magnetic fields can often be considered as decoupled. Controlled reprogramming is an example in which biological cells (and gold nanoparticles) are exposed to an external magnetic field. In contrast, tumor treating fields (TTFields) subject tumor cells to an external electric field. The controlled reprogramming of cells is an important part of regenerative medicine and a promising treatment strategy for degenerative diseases like Parkinson’s. In biological in vitro experiments with cell cultures and in some in vivo studies, it has been shown that exposure of cells in combination with gold nanoparticles (AuNPs) to magnetic fields can lead to a significant improvement in cell conversion rates. However, the initial interaction between magnetic fields and cells involving physical laws is still not fully understood. TTFields have been approved for clinical use in Germany for the treatment of glioblastoma since 2015, resulting in a relatively new treatment method for these highly malignant tumors. The effects of TTFields on tumor cells have been extensively studied in association with physical laws, but are not yet fully resolved. In this thesis, I contribute to the understanding of the initial effect of electric and magnetic fields on cells and cells with gold nanoparticles. In particular, electromagnetic parameters are examined that are typical for TTFields and cellular reprogramming. I evaluate and apply analytical and numerical methods to calculate electromagnetic field distributions. These calculations serve as the basis for the assessment of possible mechanisms of action. Furthermore, an electric lumped element model for a cell is developed which compared to other models, analytical calculations and numerical electromagnetic simulations, implifies the approximation of the relative electric field distribution in different cell layers. Additionally, to allow future consideration of electrical properties of nutrient media in calculations a capacitive measurement setup with platinum black electrodes is tested and proposed. This setup allows the determination of ion solution conductivity reliably even at relatively low frequencies around one kilohertz. In vitro cell experiments are important for the validation of theoretical results. In this regard, an improved setup for the in vitro exposure of cells to electric fields is presented, which allows the exposure of cells to more electric field polarization directions by simultaneously allowing higher electric field homogeneity. In conclusion, this thesis makes an important contribution to the field of bioelectromagnetics.