New Magnetic Nanodiscs for Non-Invasive Brain Stimulation

According to a study by MIT, new magnetic nanodiscs could offer a much less invasive way to stimulate specific brain regions. This advancement could lead to stimulation treatments that do not require implants or genetic engineering, presenting a more accessible and non-invasive approach to neurological therapies.

The tiny discs, measuring around 250 nanometers across (about 1/500 the width of a human hair), are designed to be injected directly into targeted brain regions. Once inside, they can be activated by applying a magnetic field outside the body.

These particles could soon be used in biomedical research and, after further testing, may have clinical applications. Polina Anikeeva, a professor at MIT, along with 18 other researchers from MIT and Germany, outlined the development of these nanoparticles in Nature Nanotechnology.

Deep brain stimulation (DBS) is a well-established clinical method used to alleviate symptoms of neurological and psychiatric disorders, such as obsessive-compulsive disorder and Parkinson's disease, by implanting electrodes into specific brain regions. While effective, DBS is invasive and complex, limiting its use in certain cases. The new nanodiscs could present a safer alternative for achieving similar therapeutic outcomes.

In recent years, implant-free brain stimulation techniques have emerged, but they often face limitations in spatial precision and deep brain targeting. Anikeeva's Bioelectronics group, along with others in the field, has explored the use of magnetic nanomaterials to convert external magnetic signals into brain stimulation over the past decade. However, these magnetic methods have required genetic modifications, making them unsuitable for human use.

Kim, a graduate student in Anikeeva’s group, proposed that a magnetoelectric nanomaterial capable of converting magnetization into electrical potential could enable remote magnetic brain stimulation, given that all nerve cells respond to electrical signals. However, developing such a material on a nanoscale posed significant challenges.

Kim successfully created novel magnetoelectric nanodiscs and collaborated with Noah Kent, a postdoctoral researcher in Anikeeva’s lab with a physics background and the study’s second author, to better understand their properties.

These nanodiscs consist of two layers: a magnetic core and a piezoelectric shell. The core is magnetostrictive, meaning it changes shape when magnetized, which induces strain in the piezoelectric shell and generates electrical polarization.

When exposed to magnetic fields, these particles produce electrical pulses through the combined effects of magnetostriction and piezoelectricity, stimulating neurons.

The discs' shape plays a critical role in their efficiency. Unlike previous magnetic nanoparticles, which were spherical and exhibited weak magnetoelectric effects, the anisotropic shape of the new discs enhances magnetostriction by more than a thousandfold, according to Kent.

The team first tested the nanodiscs on cultured neurons, demonstrating that short magnetic field pulses could activate the neurons without any genetic modification.

Next, they injected small amounts of nanodisc solution into targeted regions of mice's brains. By switching a nearby weak electromagnet on and off, they were able to remotely trigger electrical stimulation in the brain. Kim noted that this stimulation affected neuron activity and behavior.

The team found that these magnetoelectric nanodiscs could stimulate deep brain areas, including the ventral tegmental area, associated with reward, and the subthalamic nucleus, which plays a role in motor control.

This is the region where electrodes typically get implanted to manage Parkinson's disease.

Ye Ji Kim, Graduate Student, Massachusetts Institute of Technology

The researchers successfully demonstrated motor control modulation using the nanodiscs. By injecting the nanodiscs into only one hemisphere of the brain, they were able to induce rotational behavior in healthy mice by applying a magnetic field.

Similar to conventional implanted electrodes, which provide mild electrical stimulation, the nanodiscs could activate neuronal activity with subsecond temporal precision. However, they observed a significant reduction in foreign body responses compared to electrodes, which could make deep brain stimulation even safer.

This precise stimulation was enabled by the nanodiscs' multilayered chemical composition, unique shape, and specific dimensions.

Anikeeva noted that while the researchers achieved a significant enhancement in magnetostrictive effects—about a thousand times greater than with previous spherical particles—the conversion of this magnetic response into an electrical signal still needs improvement. The increase in electrical output was only four times higher than that of traditional particles, not fully reflecting the massive increase in magnetostriction.

Kim added, “This massive enhancement of a thousand times didn't completely translate into the magnetoelectric enhancement. That's where a lot of the future work will be focused, on making sure that the thousand times amplification in magnetostriction can be converted into a thousand times amplification in the magnetoelectric coupling.”

The team’s findings regarding the influence of particle shapes on magnetostriction were rather surprising.

It is kind of a new thing that just appeared when we tried to figure out why these particles worked so well.

Noah Kent, Postdoctoral Researcher, Massachusetts Institute of Technology

Anikeeva added, “Yes, it is a record-breaking particle, but it's not as record-breaking as it could be.”

Although that is still a work in progress, the team has ideas about how to move forward.

Large-scale safety studies are one of the additional steps that would be necessary to move these nanodiscs from basic research using animal models to clinical use in humans, “which is something academic researchers are not necessarily most well-positioned to do,” according to Anikeeva.

“When we find that these particles are really useful in a particular clinical context, then we imagine that there will be a pathway for them to undergo more rigorous large animal safety studies,” Anikeeva concluded.

Discover More: Nanodiscs: What Are They and How Are They Shaping the Future of Medicine?

Journal Reference:

Kim, Y. J. et. al. (2024) Active Fréedericksz Transition in Active Nematic Droplets. Nature Nanotechnology. doi.org/10.1101/2023.12.24.573272