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Magnetic Nanoparticles for Wireless Manipulation of Neural Circuits

Abstract:

Weak magnetic susceptibility and conductivity of biological matter suggest the application of alternating magnetic fields (AMF) with low amplitudes (~ 1-10s mT) and frequencies in the 100-kHz range for delivery of signals into deep-tissue targets. One can use nanomaterial transducers to convert the externally applied AMF into biological stimuli such as mechanical deformation or thermal perturbation. The latter can be achieved by magnetic nanoparticles 5-30 nm in diameter composed of biochemically stable and benign ferrites, such as iron oxide. When exposed to AMF with the abovementioned parameters, these MNPs undergo magnetization reversal, and the resulting hysteretic power loss is dissipated as heat. Guided by the dynamic hysteresis model, we have previously engineered a palette of ferrites and identified the AMF conditions leading to high heating efficiencies in these nanomaterials. We have then applied the concept of magnetothermal stimulation to two biological systems: wireless excitation of neural activity and remote disaggregation of amyloid beta (Aβ) deposits characteristic of Alzheimer’s disease. To enable AMF-driven neural excitation, we took advantage of a heat sensitive calcium channel TRPV1 (a capsaicin receptor), which is broadly expressed across the nervous system. We found that exposure to AMF in the presence of MNPs triggers TRPV1 and the corresponding influx of calcium ion into neurons leading to action potential firing (Figure 1). Externally controlled disruption of~ 10-µm–sized Aβ aggregates into~ 100s-nm fragments was observed when MNPs specifically targeted to Aβ via a coating with a short peptide …