CAREER: Hydrogen-Bonded Organic Frameworks Nanoparticles for Ultrasound-Activated, Genetically-Targeted Neuromodulation

NON-TECHNICAL SUMMARY

This project explores creating new nanoparticles for studying the brain. Over the last ten years, scientists have used a technique called optogenetics to understand how brains work. With optogenetics, researchers control specific brain cells using light.

The problem is that delivering this light often requires surgery, which can harm the brain's neurons. Instead, the team is developing nanoparticles and using ultrasound waves to achieve the same results without surgery. These nanoparticles, made of special materials called hydrogen-bonded organic frameworks, can emit light or release chemicals when hit by ultrasound waves.

By altering the molecules inside them, the color of the emitted light changes after ultrasound exposure. Also, altering the nanoparticle structures allows control over the amounts of released chemicals upon ultrasound impact. The resulting light or chemicals can control certain brain neurons without harming the brain tissues.

Beyond the science, the project includes an outreach program named "Biomaterials Research in Engineering." It aims to get Austin Community College students more interested in engineering, especially those who have not considered it before. Through a mix of theory and hands-on activities, the program seeks to spark interest and improve diversity in engineering fields.

By overcoming current method challenges, this research not only increases scientific knowledge of hydrogen-bonded organic frameworks nanoparticles but also develops better technologies for understanding and treating brain diseases. The inclusion of the outreach program reflects a commitment to diversity and inclusion in engineering fields, crucial for the long-term health and innovation of the scientific community.

TECHNICAL SUMMARY

This research project aims to advance the fields of optogenetics and chemogenetics through the innovative development of hydrogen-bonded organic frameworks (HOFs) nanoparticles for ultrasound-triggered neuromodulation. Existing challenges in optogenetics, notably the necessity for invasive optical fiber implantation, emphasize the need for exploring sono-optogenetics, a paradigm where nanoparticles are activated by focused ultrasound (FUS).

The envisioned HOFs nanoparticles, intricately assembled through multi-hydrogen bonds and π-π stacking are desirable for achieving non-invasive optogenetic and chemogenetic control over neural activity. An important goal is to design a versatile emission platform of luminophores activated by ultrasound, for control of multi-colored opsins in optogenetics.

Furthermore, the research outlines the customization of HOFs nanoparticles for precise and controlled ultrasound-triggered drug release in chemogenetics. The key focus lies in manipulating cohesive energy by modulating the number of hydrogen bonds and π-π interactions within the HOFs structure, presenting an innovative approach to achieving programmable drug delivery.

The proposed technical approach not only expands our understanding of HOFs as biomaterials but also holds the potential to significantly impact neuroscience research and therapeutic interventions for neurological diseases. Beyond its technical scope, this project incorporates a significant broader impact through the initiation of the "biomaterials research in engineering" (BRING) outreach program.

This program is designed to engage underrepresented engineering students at Austin Community College (ACC) in theoretical and practical modules related to biomaterials research. This research has a profound impact on advancing our fundamental understanding of HOFs as biomaterials, thereby influencing the development of technologies for neuroscience research and therapeutic applications in neurological diseases.

The involvement of science, technology, engineering and mathematics (STEM) students, particularly those underrepresented at ACC, aligns with a broader commitment to promoting diversity and inclusion in the scientific community.

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.