Nerve cells are the messengers between the brain and the rest of the body, so when they misfire, the results can be catastrophic and hard to treat. One common outcome is neuropathic pain, also known as nerve pain, which occurs when damaged or irritated nerve cells become overactive, sending a persistent “false alarm” to the brain in the form of pain signals.
Nerve pain is estimated to affect as many as 1 in 10 adults. Many turn to opioids for effective pain management, which can lead to dependence.
Another manifestation is epilepsy, which is caused by neurons in the brain misfiring and creating abnormal bursts of electrical activity. For patients with epilepsy and other conditions characterized by overactive nerve cells, deep brain stimulation can offer relief, but it requires invasive surgery to place electrodes inside the brain.
A team of researchers from the Margie and Bill Klesse College of Engineering and Integrated Design at UT San Antonio aims to give patients a better treatment option: a noninvasive, wireless platform that can send treatment instructions into the brain from outside the body using magnetic signals. The technology is opening new doors for treating neuropathic pain, epilepsy and other complex conditions.
Led by Gabriela Romero Uribe, PhD, Endowed USAA Distinguished Professor in the Department of Biomedical and Chemical Engineering, the team designs smart nanomaterials engineered at the scale of just 20 nanometers.
A tiny translator for brain signals
To bypass the need for surgery, Romero Uribe’s team uses tailor-made magnetic nanoparticles and controls them remotely with magnetic fields. Once inside the body, the nanoparticles remain inactive at normal body temperatures until an external magnetic field is applied.
When exposed to an alternating magnetic field (AMF) from outside the body, the particles undergo “hysteresis heating,” a phenomenon that happens when the magnetic orientation attempts to follow the changing field.
“We like to use magnetic fields because biological tissues do not block them, and we don’t need wires or batteries implanted inside the body,” Romero Uribe explained.
To leverage this heat for targeted medical treatment, the team coats the nanoparticles with a temperature-sensitive polymer. When the magnetic field is turned on, the temperature shift collapses the polymer coating, releasing precise doses of medication directly at the target cell membrane. When the external device is turned off, the polymer expands, re-sealing the coating and pausing the drug delivery until the next treatment cycle.
“We look at the nanoparticles as translators, translating an external signal into a signal that cells can recognize — which could be electricity or a chemical compound,” Romero Uribe added.
Pain relief without opioids
This intricate chain reaction could be harnessed to treat a range of conditions, but one of Romero Uribe’s first targets was neuropathic pain.
Her team, including UT San Antonio PhD candidate Athena Santi and Amanda Gomez, ’26, PhD, loaded the polymer-coated magnetic nanoparticles with capsaicin, the natural compound that gives chili peppers their heat. Capsaicin selectively targets a key pain-sensing receptor found on nerve cells called Transient Receptor Potential Vanilloid 1 (TRPV1).
While a single dose of capsaicin excites the receptor and triggers a burning sensation, repeated or “tonic” microdosing desensitizes the channel, effectively numbing the nerve cell to future pain signals.
A preclinical study showed that delivering repeated magnetic pulses desensitized the receptors in more than 90% of the neurons, shutting down their ability to transmit pain signals.
Dual-action control for complex conditions
Through continuous testing and fine-tuning, Romero Uribe aims to address more complex conditions like epilepsy, which involve hyperexcitable brain circuits.
Calming a complex brain disorder often requires more than a single command. To address this, the lab is engineering nanoparticles with two distinct polymer coatings that collapse at different trigger temperatures — one at 40°C and another at 60°C.
By tuning the magnetic field strength, the researchers can independently release two different drugs from the same system: an excitatory agent (such as bay-K8644) to wake up specific cells, or an inhibitory agent (such as verapamil) to calm overactive circuits.
“With complex conditions like pain or epilepsy, the cells are too active in part because the surrounding inhibitory networks aren’t working properly,” Romero Uribe noted. “If you want to tackle a problem like that, simply inhibiting one circuit isn’t enough. You have to activate some cells and calm others simultaneously.”
To bring the technology one step closer to clinical use, the team is testing these nanoparticle systems on human brain organoids — three-dimensional, lab-grown human brain tissue models that allow for personalized medicine research.
Romero Uribe’s research is supported by a National Science Foundation (NSF) CAREER Award and done in collaboration with Brain Health Consortium Director Jenny Hsieh, PhD, as well as the Stem Cell Core at UT San Antonio.
