Neuromodulation approaches available to the neuroscience community are either mechanically invasive (electrical stimulation), require transgenes (e.g. optogenetics, DREADDs), or lacking the resolution and cell-type specificity (ultrasound, transcranial magnetic stimulation). In our group we explore magnetic nanomaterials as transducers of wireless magnetic neuromodulation (Science, 2015). Due to its negligible magnetic susceptibility and low conductivity, biological matter is nearly transparent to weak magnetic fields (MFs) in alternating the low radiofrequency range (10s of kHz to 10s of MHz). Furthermore, it is well known in the field of cancer hyperthermia that magnetic nanoparticles (MNPs, 5-30 nm in diameter) can dissipate significant heat via hysteretic power loss in MFs. We leveraged this local heating to trigger heat-sensitive ion channels genetically introduced (Science 2015) or naturally present in electroactive cells (Sci. Adv. 2020). To achieve efficient heat dissipation and thus rapid neuronal activation, we have synthesized a broad palette of tertiary magnetic oxides with coercivities varying across three orders of magnitude (ACS Nano 2013; Nano Lett. 2016) and developed a model for dynamic hysteresis in magnetic nanomaterials, which allowed us to tailor the conditions of alternating MF (Rev. Sci. Instr. 2017) to the MNP properties. The latter lead to the idea of magnetothermal multiplexing (Appl. Phys. Lett. 2014; Adv. Funct. Mater. 2020): the ability to independently heat (collocated) MNPs with different magnetic properties by using alternating MFs with distinct amplitudes and frequencies – a concept previously overlooked due to the use of linear models of hysteresis.
In addition to thermal stimulation of neural activity, we are leveraging hysteretic heat dissipation to enable local magnetically-driven delivery of pharmacological compounds to the membranes of neurons (Adv. Funct. Mater. 2016). This concept was further generalized by encapsulating MNPs within thermo-sensitive liposomes that releases their pharmacological payloads in response to the remotely applied MFs. Loaded with ligands for the natural or engineered receptors, these magneto-liposomes could mediate local chemomagnetic modulation of neuronal activity, enabling wireless control of mouse behavior in assays of sociability and motivation (Nat. Nanotechnol. 2019).
Finally, we are exploring alternative means for using magnetic nanomaterials for neuromodulation, for example we are developing magnetic nanodiscs as transducers of mechanical stimuli under slow-varying MFs. Mechanical transduction mediated by magnetic nanomaterials demands either large MF gradients (~100 T/m) or particles with large magnetic moments. While the former is impractical in behaving subjects, the latter presents a challenge due to dipole-dipole interactions between single particle magnetic moments that render them colloidally unstable in solutions. We have addressed this challenge by developing anisotropic nanodiscs that in the absence of magnetic fields support a magnetic vortex state with zero net magnetization ensuring their colloidal stability. Upon application of weak, slow varying MFs, these particles assume in-plane magnetization and transduce torques to the cell membranes proportional to their magnetic volumes (ACS Nano 2020).