Dekel Rosenfeld1 Alexander Senko2 Michael Christiansen1 2 Junsang Moon2 Danijela Gregurec1 Alik Widge3 4 Polina Anikeeva1 2

1, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States
2, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States
3, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States
4, MGH, Cambridge, Massachusetts, United States

Magnetic nanoparticles (MNPs) dissipate heat upon exposure to alternating magnetic fields (AMFs), which then can trigger thermally-sensitive ion channels in electro-active cells such as neurons. In mammals, peripheral nerve fibers express heat-sensitive cation channels from the transient receptor potential family. Consequently, local heating from MNPs can be converted into an electrochemical gradient across the neural membranes, leading to depolarization and firing of action potentials in response to the externally applied AMF. The use of MNPs eliminates the need for invasive and tissue-damaging electrodes. Moreover, AMF has higher penetration depth (>10cm) compared to other methods and therefore is more suitable for deep tissue stimulation. Previously, MNPs were primarily used to trigger heat-sensitive ion channels in neurons. However, it has been shown that heat sensitive ion channels, such as TRPV1, exist also in other tissues, for example in the adrenal gland. Abnormal regulations of hormones produced within the glands have been linked to altered stress responses in patients suffering from mental disease. The adrenal gland is therefore a high-value target for peripheral neuromodulation and control of hormones. We employed iron oxide MNPs 22 nm exposed to AMF to trigger hormone release from adrenal glands in vivo. Iron oxide MNPs were synthesized and surface functionalization was conducted by polymeric coating with polyethylene glycol. The size, concentration, saturation magnetization, and specific loss power of the MNPs were examined and tailored to the applied AMF. Adrenal cell culture was shown to respond robustly to magnetothermal stimulation. MNPs location of injection, concentration and volume was determined by a finite element model showing the heat distribution within the adrenal gland under the applied AMF. In order to investigate the response of adrenal gland to magnetothermal stimulation in vivo, a custom AMF apparatus including a resonant tank circuit was developed. The effects of magnetothermal adrenal stimulation were assessed in live rats by hormone levels in the rat blood comparing the levels before and after stimulation.