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In Vivo Wireless Brain Stimulation via Non-invasive and Targeted Delivery of Magnetoelectric Nanoparticles

Abstract

Wireless and precise stimulation of deep brain structures could have important applications to study intact brain circuits and treat neurological disorders. Herein, we report that magnetoelectric nanoparticles (MENs) can be guided to a targeted brain region to stimulate brain activity with a magnetic field. We demonstrated the nanoparticles’ capability to reliably evoke fast neuronal responses in cortical slices ex vivo. After fluorescently labeled MENs were intravenously injected and delivered to a targeted brain region by applying a magnetic field gradient, a magnetic field of low intensity (350–450 Oe) applied to the mouse head reliably evoked cortical activities, as revealed by two-photon and mesoscopic imaging of calcium signals and by an increased number of c-Fos expressing cells after stimulation. Neither brain delivery of MENs nor the magnetic stimulation caused significant increases in astrocytes and microglia. Thus, MENs could enable a non-invasive and contactless deep brain stimulation without the need of genetic manipulation.

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Acknowledgements

We thank Tiffany Stewart, Wenhui Xiong, and Xingjie Ping for their experimental support.

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Funding

This publication was made possible with partial support from the N3 program of the DARPA of the Department of Defense (SK, XJ, and LP), the National Science Foundation (NSF) under the grant number ECCS-1935841 (SK and XJ), and from the pre-doctoral fellowship to TN of National Institute of Health grant number NIH-UL1TR002529 (A. Shekhar, PI), National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award, and the Indiana University Department of Medicine.

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X. Jin and S. Khizroev conceived the project, designed the experiments, discussed the data, and wrote the manuscript. T. Nguyen designed and performed the experiments, analyzed the data, and wrote the manuscript. S. Khizroev, P. Liang, P. Wang, and A. Nagesetti synthesized and characterized the nanoparticles. P. Andrews, S. Masood, Z. Vriesman, and J. Gao performed the experiments and analyzed the data.

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Correspondence to Xiaoming Jin.

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Nguyen, T., Gao, J., Wang, P. et al. In Vivo Wireless Brain Stimulation via Non-invasive and Targeted Delivery of Magnetoelectric Nanoparticles. Neurotherapeutics (2021). https://doi.org/10.1007/s13311-021-01071-0

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Keywords

  • Noninvasive brain stimulation
  • Nanoparticles
  • Calcium imaging
  • Two-photon
  • Neuroinflammation