High frequency (HF) electromagnetic fields (EMFs) have been widely used in many wireless communication devices, yet within the terahertz (THz) range, their effects on biological systems are poorly understood. In this study, electromagnetic radiation in the range of 0.3-19.5 x 10 12 Hz, generated using a synchrotron light source, was used to investigate the response of PC 12 neuron-like pheochromocytoma cells to THz irradiation. The PC 12 cells remained viable and physiologically healthy, as confirmed by a panel of biological assays; however, exposure to THz radiation for 10 min at 25.2 ± 0.4 ◦ C was sufficient to induce a temporary increase in their cell membrane permeability. High-resolution transmission electron microscopy (TEM) confirmed cell membrane permeabilization via visualisation of the translocation of silica nanospheres (d = 23.5 ± 0.2 nm) and their clusters (d = 63 nm) into the PC 12 cells. Analysis of scanning electron microscopy (SEM) micrographs revealed the formation of atypically large (up to 1 µm) blebs on the surface of PC 12 cells when exposed to THz radiation. Long-term analysis showed no substantial differences in metabolic activity between the PC 12 cells exposed to THz radiation and untreated cells; however, a higher population of the THz-treated PC 12 cells responded to the nerve growth factor (NGF) by extending longer neurites (up to 0-20 µm) compared to the untreated PC12 cells (up to 20 µm). These findings present implications for the development of nanoparticle-mediated drug delivery and gene therapy strategies since THz irradiation can promote nanoparticle uptake by cells without causing apoptosis, necrosis or physiological damage, as well as provide a deeper fundamental insight into the biological effects of environmental exposure of cells to electromagnetic radiation of super high frequencies
