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

该项目探索创造用于研究大脑的新型纳米颗粒。在过去的十年里，科学家们使用了一种叫做光遗传学的技术来了解大脑是如何工作的。通过光遗传学，研究人员利用光控制特定的脑细胞。问题是，传递这种光通常需要手术，这可能会损害大脑的神经元。相反，该团队正在开发纳米颗粒，并使用超声波来达到相同的效果，而无需手术。这些纳米粒子是由一种叫做氢键有机框架的特殊材料制成的，当受到超声波的撞击时，它们可以发光或释放化学物质。通过改变它们内部的分子，超声波照射后发出的光的颜色会发生变化。此外，改变纳米粒子的结构可以控制在超声波冲击下释放的化学物质的数量。由此产生的光或化学物质可以在不伤害脑组织的情况下控制某些大脑神经元。除了科学研究，该项目还包括一个名为“工程生物材料研究”的拓展项目。它的目的是让奥斯汀社区学院的学生对工程学更感兴趣，尤其是那些以前没有考虑过工程学的学生。通过理论和实践活动的结合，该计划旨在激发人们的兴趣，提高工程领域的多样性。通过克服现有方法的挑战，本研究不仅增加了对氢键有机框架纳米粒子的科学知识，而且还开发了更好的技术来理解和治疗脑部疾病。外展计划的纳入反映了对工程领域多样性和包容性的承诺，这对科学界的长期健康和创新至关重要。本研究项目旨在通过创新开发用于超声触发神经调节的氢键有机框架（HOFs）纳米颗粒，推动光遗传学和化学遗传学领域的发展。光遗传学中存在的挑战，特别是侵入性光纤植入的必要性，强调了探索声光遗传学的必要性，声光遗传学是一种通过聚焦超声（FUS）激活纳米颗粒的范例。设想的hof纳米颗粒通过多氢键和π-π堆叠复杂地组装，对于实现对神经活动的非侵入性光遗传学和化学遗传学控制是理想的。一个重要的目标是设计一个由超声激活的多功能发光团发射平台，用于光遗传学中多色视蛋白的控制。此外，该研究概述了在化学遗传学中精确控制超声触发药物释放的HOFs纳米颗粒的定制。重点在于通过调节hof结构内的氢键和π-π相互作用的数量来操纵内聚能，提出了一种实现可编程给药的创新方法。所提出的技术方法不仅扩展了我们对hof作为生物材料的理解，而且还具有显著影响神经科学研究和神经系统疾病治疗干预的潜力。在其技术范围之外，该项目通过启动“工程生物材料研究”（BRING）外展计划，具有重要的更广泛的影响。本课程旨在吸引奥斯汀社区学院（ACC）未被充分代表的工程专业学生参与与生物材料研究相关的理论和实践模块。这项研究对推进我们对hof作为生物材料的基本认识产生了深远的影响，从而影响了神经科学研究和神经疾病治疗应用技术的发展。科学、技术、工程和数学（STEM）学生的参与，特别是那些在ACC中代表性不足的学生的参与，与促进科学界多样性和包容性的更广泛承诺是一致的。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

NON-TECHNICAL SUMMARYThis 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 SUMMARYThis 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.