Innovative magnetic nanodiscs might offer a significantly less invasive approach for brain stimulation, leading to treatment options that don’t require implants or genetic alterations, as reported by researchers from MIT.
The researchers believe that these tiny discs, measuring around 250 nanometers in diameter (roughly 1/500th the thickness of a human hair), could be injected directly into targeted areas of the brain. Once injected, they can be activated at any moment through the application of a magnetic field from outside the body. These new particles may soon find applications in biomedical research, and with sufficient testing, could be adopted for clinical use.
The findings about these nanoparticles are detailed in the journal Nature Nanotechnology, in a study authored by Polina Anikeeva, a professor at MIT in Materials Science and Engineering and Brain and Cognitive Sciences, along with graduate student Ye Ji Kim and 17 others from both MIT and Germany.
Deep brain stimulation (DBS) is a widely accepted clinical method where electrodes are implanted in specific brain regions to alleviate symptoms of neurological and psychiatric disorders such as Parkinson’s disease and obsessive-compulsive disorder. Although DBS is effective, the challenges of surgery and potential complications limit its applicability. The newly developed nanodiscs could offer a much less invasive alternative to achieve similar outcomes.
In recent years, various alternative non-invasive methods for brain stimulation have emerged. However, many of these techniques struggled with precise targeting of deeper brain regions. For the last decade, Anikeeva’s Bioelectronics group and others have attempted to use magnetic nanomaterials to convert external magnetic signals into brain stimulation. Unfortunately, these methods necessitated genetic modifications, making them unsuitable for human applications.
Given that all nerve cells react to electrical signals, Kim, a graduate student in Anikeeva’s lab, proposed that a magnetoelectric nanomaterial capable of efficiently transforming magnetization into electrical potential could lead to a viable method of remote magnetic brain stimulation. However, creating such nanoscale magnetoelectric materials proved to be a tough challenge.
Kim went on to create innovative magnetoelectric nanodiscs and partnered with Noah Kent, a postdoctoral researcher in Anikeeva’s lab who specializes in physics, to investigate the properties of these particles.
The structure of the new nanodiscs features a two-layer magnetic core encased in a piezoelectric shell. The magnetic core exhibits magnetostriction, meaning it changes shape when exposed to a magnetic field. This transformation induces strain in the piezoelectric shell, leading to fluctuating electrical polarization. By combining these two effects, the composite particles can deliver electrical signals to neurons in response to magnetic fields.
A key factor in the effectiveness of these discs is their shape. Prior attempts utilized spherical magnetic nanoparticles which exhibited a weak magnetoelectric effect, according to Kim. The new disc shape enhances magnetostriction by more than 1000 times, as noted by Kent.
The researchers began by introducing the nanodiscs to cultured neurons, enabling them to stimulate these cells on demand using brief magnetic field pulses. Notably, this stimulation did not require any genetic alterations.
They subsequently injected small amounts of the magnetoelectric nanodiscs solution into targeted regions of mice brains. By activating a relatively weak nearby electromagnet, the particles released a minor electrical impulse in the specific brain area. This stimulation could be toggled on and off remotely by switching the electromagnet. According to Kim, this electrical activity “affected neuron function and behavior.”
The research team discovered that the magnetoelectric nanodiscs could stimulate deep brain regions, specifically the ventral tegmental area, which is linked to feelings of reward.
They also targeted another crucial area, the subthalamic nucleus, which is associated with motor control. “This is the area where electrodes are usually implanted to address Parkinson’s disease,” Kim explains. The researchers successfully demonstrated their ability to modulate motor control using the nanodiscs. By injecting them into only one side of the brain, they were able to induce rotations in healthy mice through the application of a magnetic field.
The nanodiscs stimulated neuronal activity comparable to conventional implanted electrodes delivering mild electrical signals. The authors achieved rapid temporal precision for neural stimulation using this method and noted significantly lower foreign body responses compared to traditional electrodes, potentially enhancing the safety profile of deep brain stimulation.
The unique chemical structure and physical characteristics of these multilayered nanodiscs are what made precise stimulation feasible.
While the researchers successfully improved the magnetostrictive effect, the second part of the process—transforming the magnetic effect into an electrical output—still requires further enhancements, according to Anikeeva. Despite the magnetic response being a thousand times stronger, the conversion to electrical impulses was only four times greater than that achieved with standard spherical particles.
“This tremendous increase of a thousand times has not fully translated into enhanced magnetoelectric output,” states Kim. “This area will be a key focus for future research, ensuring that the substantial amplification in magnetostriction translates into equivalent enhancement in magnetoelectric coupling.”
The unexpected findings about how the shapes of the particles impact their magnetostriction were quite surprising to the team. “It’s an entirely new aspect that emerged when we investigated the effectiveness of these particles,” Kent remarks.
Anikeeva notes, “Yes, we have a groundbreaking particle, but it still holds potential for even greater advancements.” This remains a topic for ongoing research, with the team generating ideas for future progress.
While these nanodiscs could theoretically be utilized for fundamental research in animal models, translating them for use in humans would necessitate several additional steps, including extensive safety evaluations, as Anikeeva points out. “When we verify that these particles are truly beneficial in a specific clinical context, we anticipate pathways for them to undergo more thorough safety trials in larger animal studies.”
The research team included members from MIT’s departments of Materials Science and Engineering, Electrical Engineering and Computer Science, Chemistry, and Brain and Cognitive Science; the Research Laboratory of Electronics; the McGovern Institute for Brain Research; and the Koch Institute for Integrative Cancer Research, in addition to collaborators from Friedrich-Alexander University of Erlangen, Germany. This study received support from the National Institutes of Health, the National Center for Complementary and Integrative Health, the National Institute for Neurological Disorders and Stroke, the McGovern Institute for Brain Research, and the K. Lisa Yang and Hock E. Tan Center for Molecular Therapeutics in Neuroscience.
