# Non-invasive, Transgene-free, on-demand Pharmacological Modulation of Neural Activity

> **NIH NIH R21** · UNIVERSITY OF TEXAS SAN ANTONIO · 2021 · $176,500

## Abstract

PROJECT SUMMARY/ABSTRACT
Cell-type specific manipulation of neural circuits is required for the treatment of neurological disorders such as
epilepsy and autism. Existing technologies to control neural activity offer limited possibilities. Manipulation of
brain circuits via direct drug treatment is restricted by the selective permeability of the blood-brain barrier, the
rapid clearance of cerebral fluids and the lack of specificity, which results in poor response to drugs and
undesirable side effects. Electrical stimulation and optogenetics have open the possibility of repairing neural
dysfunction through direct control of brain circuit dynamics. However, both technologies require implantable
devices that are damaging to biological tissues. Recently, the heat dissipation by nanomaterials, particularly
magnetic nanoparticles (MNPs) and plasmonic nanostructures, has been proposed for the wireless control of
cellular signaling using external stimuli. The weak magnetic properties and low electrical conductivity of tissue
allow alternating magnetic fields (AMFs) to reach deep into the body, making hysteresis heating of MNPs
particularly promising for the treatment of brain disorders. This research grant will develop a novel wireless
pharmacological brain modulation approach that depends on MNPs heating effects to release
neuromodulatory compounds from temperature-sensitive polymers grafted on the surface of MNPs.
Additionally, we will fabricate a nanoconjugate composed of surface engineered MNPs and gold nanorods
(GNRs) for photoacoustic tomography (PAT)-guided, magnetothermally-controlled release of neuromodulatory
compounds. Preliminary results demonstrate: 1) the heat dissipated by MNPs under AMFs is sufficient for the
complete release of a payload from MNP surfaces, 2) MNPs targeting to neuronal membranes via antibody
specificity, followed by magnetothermal drug treatment that allows for excitation of neural activity, and 3) the
precise control of polymer growth from the surface of MNPs. This research grant drives new advances in stimuli-
responsive hybrid nanoparticle systems for personalized pharmacological modulation of neural activity. Wireless
magnetothermal release of dopamine and chlorpromazine from polymer coated MNPs is expected to excite and
inhibit activity of dopaminergic neurons. Taking advantage of GNRs-mediated PAT, this system will be
customized for on-demand release in multiple dosages by triggering heat response with AMFs. Finally, the
functional properties of clinically-relevant neural modulation by magnetothermal drug release will be evaluated
through in vitro models and rat brains. Magnetothermal modulation of neural activity shows considerable promise
as a powerful pharmacological technology that can be applied to restore brain functions, and in single-cell
manipulation settings for the better understanding of neural circuits. Future directions of this work include the
development of a magnetothermal platform that allow in viv...

## Key facts

- **NIH application ID:** 9892391
- **Project number:** 1R21NS111185-01A1
- **Recipient organization:** UNIVERSITY OF TEXAS SAN ANTONIO
- **Principal Investigator:** Gabriela Romero Uribe
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $176,500
- **Award type:** 1
- **Project period:** 2021-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9892391

## Citation

> US National Institutes of Health, RePORTER application 9892391, Non-invasive, Transgene-free, on-demand Pharmacological Modulation of Neural Activity (1R21NS111185-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9892391. Licensed CC0.

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