Localized Excitation of Neural Activity via Rapid Magnetothermal Drug Release

Hysteretic heat dissipation by magnetic nanoparticles (MNPs) in alternating magnetic fields (AMFs) allows these materials to act as local transducers of external stimuli. Commonly employed in cancer research, MNPs have recently found applications in remote control of heat-dependent cellular pathways. Here, a thermally labile linker chemistry is adapted for the release of neuromodulatory compounds from the surfaces of MNPs via local nanoscale heating. By examining a range of MNP sizes, and considering individual particle loss powers, AMF conditions and nanomaterials suitable for rapid and complete release of a payload from MNP surfaces are selected. Local release of allyl isothiocyanate, an agonist of the Ca2+ channel TRPV1 (transient receptor potential vanilloid cation channel subfamily member 1), from iron oxide MNPs results in pharmacological excitation of neurons with latencies of approximate to 12 s. When targeted to neuronal membranes, these MNPs trigger Ca2+ influx and action potential firing at particle concentrations three orders of magnitude less than those previously used for magnetothermal neuromodulation accomplished with bulk heating.