(446e) Non-Invasive Excitation and Inhibition of Neural Activity Via on-Demand Magnetothermal Drug Release

Cell-type specific manipulation of neural circuits is required for the treatment of neurological disorders such as epilepsy and Parkinson’s disease. Precise control of neural circuits will enable the development of neuromodulation therapies for these debilitating conditions. Existing technologies to control neural activity offer limited possibilities. Manipulation of brain circuits via direct drug treatment is restricted by the selective permeability of the blood-brain barrier, the rapid clearance of cerebral fluids and the lack of specificity which results in poor response to drugs and undesirable side effects. Electrical stimulation and optogenetics have open the possibility of repairing neural dysfunction through direct control of brain circuit dynamics. However, both technologies require implantable devices that are damaging to biological tissues. Recently, the heat dissipation by nanomaterials, particularly magnetic nanoparticles (MNPs) and plasmonic nanostructures, has been proposed for the wireless control of cellular signaling using external stimuli. The weak magnetic properties and low electrical conductivity of tissue allow alternating magnetic fields (AMFs) to reach deep into the body, making hysteresis heating of MNPs particularly promising for the treatment of brain disorders. Here, we developed a novel wireless pharmacological brain stimulation approach that depends on magnetic nanoparticles (MNPs) heating effects to release neuromodulatory compounds from temperature-sensitive polymers grafted on the surface of MNPs. The developed technology is suitable for drug release in multiple on-demand dosages, which it is required for neural activity stimulation. Additionally, we tailor polymer surface chemistry for the combinatorial release of neurostimulator-inhibitor pairs to allow modulation of brain circuit signals. This work drives new advances in stimuli-responsive hybrid nanoparticle systems for the pharmacological modulation of neural activity. Wireless magnetothermal release of dopamine and chlorpromazine from polymer coated MNPs is used to excite and inhibit activity of striatal neurons. This system is optimized for on-demand multiple dosages release by triggering heat response with AMFs. Magnetothermal modulation of neural activity shows considerable promise as a powerful pharmacological technology that can be applied to restore brain functions, and in single-cell manipulation settings for the better understanding of neural circuits. Future directions of this work include the development of a magnetothermal platform that allow in vivo pharmacological modulation of neural activity.