CAREER: Tailoring Thermal Conductivity of Soft Magnetic Nanomaterials for Wireless Neuromodulation

The treatment of neurological disorders and psychiatric conditions requires precise control of neural cell signaling; however, existing technologies to control neural activity lack specificity or are damaging to brain tissues, causing undesirable side effects. This NSF CAREER project aims to develop a new nanotechnology to selectively control neural activity for the next generation of brain malfunction therapies, e.g., the treatment of epilepsy.

The project will (1) lead to a completely new paradigm for the precise control of neural activity, (2) provide the research community with a new platform for mapping brain circuits to improve our understanding of complex neural networks, (3) enable the on-demand localized release of drugs required for the next generation of therapies, and (4) accelerate the development of wireless technologies for the treatment of brain malfunctions. As part of an education objective to integrate this research into an educational program designed to increase student interest and improve performance in STEM fields, the investigator will (1) develop new student-centered learning activities to promote metacognition (“learning to learn”) in undergraduate Biotransport Phenomena education, (2) provide research access and training in nanoscale heat and mass transport to local high school teachers, (3) create developmentally appropriate standards-based high school activities and lessons reaching to approximately 2,000 local high school students in San Antonio and (4) continue to recruit and mentor underrepresented minority students in engineering by serving as a Latina role model in academia.

The investigator’s long-term research goal is to build an innovative and productive research program to investigate nanoscale transport phenomena principles for the development of novel neuromodulation and new nanotechnological platforms to revolutionize the precise control of neural networks. Toward this goal, this CAREER project will develop a soft magnetic nanomaterials platform to enable a stable pharmacological, non-toxic, targetable strategy for neuromodulation by transducing alternating magnetic fields into chemical stimulus.

The project addresses the need for a technique for evoking and inhibiting neural activity on demand to understand the basic biology of neural circuit dynamics that considers cell-type specificity but does not require pharmacological agents, delivery of transgenes, or implantable devices that are damaging to biological tissue. This will be accomplished by surface engineering magnetic nanoparticles (MNPs) with biocompatible temperature responsive polymer brushes loaded with neuromodulatory compounds.

The heat generated by the MNPs under alternating magnetic fields (AMFs) will trigger conformational changes in their polymer coating releasing loaded neuromodulators. The local release of neuromodulatory compounds will enhance or inhibit specific cell membrane receptors inducing neural depolarization. The system will be investigated for the possible management of epileptic seizures by modulating hippocampal neural activity on-demand through the local release of verapamil and bay-K8644 from MNPs targeted to the cell membrane.

The research plan is organized under three aims: (1) Investigate the synthesis and characterization of biocompatible temperature-responsive polymer brushes, (2) Investigate polymer brushes coatings on magnetic nanoparticles surface for the entrapment of neuromodulatory compounds and its on-demand release, and (3) Design a magnetothermal pharmacological paradigm for precise modulation of neural activity,

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.