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

非技术总结这个项目探索创造用于研究大脑的新纳米颗粒。在过去的十年里，科学家们使用了一种名为光遗传学的技术来了解大脑是如何工作的。通过光遗传学，研究人员可以利用光来控制特定的脑细胞。问题是，传递这种光通常需要手术，这可能会损害大脑神经元。相反，该团队正在开发纳米颗粒，并使用超声波在不进行手术的情况下获得同样的结果。这些纳米颗粒由称为氢键有机骨架的特殊材料制成，当受到超声波打击时，可以发出光或释放化学物质。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，改变纳米颗粒的结构可以控制超声波撞击时释放的化学物质的量。由此产生的光线或化学物质可以控制某些脑神经元，而不会损害脑组织。除了科学之外，该项目还包括一个名为“生物材料工程研究”的外展项目。它旨在让奥斯汀社区学院的学生对工程学更感兴趣，特别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，该项目寻求激发人们的兴趣，提高工程领域的多样性。通过克服目前的方法挑战，这项研究不仅增加了氢键有机骨架纳米粒子的科学知识，还开发了更好的理解和治疗脑部疾病的技术。推广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。技术总结该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骨架(Hofs)纳米颗粒来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，特别是有创光纤植入的必要性，强调了探索声光遗传学的必要性，这是一种通过聚焦超声(FUS)激活纳米颗粒的范例。设想的Hofs纳米颗粒，通过多氢键和π-π堆积复杂组装，是实现对神经活动的非侵入性光发生和化学发生控制的理想选择。一个重要的目标是设计一个由超声波激活的发光体的通用发射平台，以控制光遗传学中的多色视蛋白。此外，该研究还概述了在化学遗传学中为精确和受控的超声触发药物释放定制Hofs纳米颗粒。重点在于通过调节HOFS结构中的氢键和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药物递送的创新方法。拟议的技术方法不仅扩大了我们对Hofs作为生物材料的理解，而且有可能对神经科学研究和神经系统疾病的治疗干预产生重大影响。除了技术范围之外，该项目还通过启动“工程中的生物材料研究”(BOW)推广计划产生了重大而广泛的影响。该项目旨在让奥斯汀社区学院(ACC)未被充分代表的工程学学生参与与生物材料研究相关的理论和实践模块。这项研究对促进我们对Hofs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，符合促进科学界多样性和包容性的更广泛承诺。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.