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

职业：用于超声激活、基因靶向神经调节的氢键有机框架纳米颗粒

• 批准号: 2340964
• 负责人: Huiliang Wang
• 金额: $ 50.83万
• 依托单位: University of Texas at Austin
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2024
• 资助国家: 美国
• 起止时间: 2024-06-01 至 2029-05-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2340964&HistoricalAwards=false
• 关键词: CAREER; Hydrogen; Bonded; Organic; Frameworks

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.

非技术总结项目探讨了创建用于研究大脑的新纳米颗粒。在过去的十年中，科学家使用了一种称为光遗传学的技术来了解大脑的工作原理。使用光遗传学，研究人员使用光控制特定的脑细胞。问题在于，传递此光通常需要手术，这可能会损害大脑的神经元。取而代之的是，该团队正在开发纳米颗粒，并使用超声波在不手术的情况下实现相同的结果。这些纳米颗粒由特殊材料制成，称为氢键有机框架，当被超声波击中时，可以发出光或释放化学物质。通过改变它们内部的分子，超声暴露后发出的光的颜色变化。同样，改变纳米颗粒结构可以控制超声冲击时释放的化学物质的量。所得的光或化学物质可以控制某些脑神经元而不会损害脑组织。除了科学外，该项目还包括一个名为“工程生物材料研究”的外展计划。它的目的是使奥斯汀社区大学的学生对工程更感兴趣，尤其是那些以前从未考虑过的人。通过理论和动手活动的混合，该计划试图激发工程领域的兴趣并提高多样性。通过克服当前方法的挑战，这项研究不仅增加了氢键有机框架纳米颗粒的科学知识，而且还开发了更好的理解和治疗脑疾病的技术。外展计划的包含反映了对工程领域的多样性和包容性的承诺，对于科学界的长期健康和创新至关重要。技术摘要摘要旨在通过氢键键入的有机框架（Hofs）Nananoptripe的创新开发来推进光遗传学和化学遗传学的领域。现有的光遗传学挑战，尤其是侵入性光纤植入所必需的，强调需要探索Sono-Optogenetics，这是一种范式，其中纳米颗粒被聚焦超声（FUS）激活。通过多氢键和π-π堆积精致组装的设想的HOF纳米颗粒对于实现神经元活性的非侵入性光遗传学和化学遗传控制是必需的。一个重要的目标是设计由超声激活的发光器的多功能发射平台，以控制光遗传学中的多色opsins。此外，该研究概述了HOFS纳米颗粒的定制，以精确并受控超声触发的药物释放化学遗传学。关键重点在于通过调节HOFS结构内的氢键和π-π相互作用的数量来操纵凝聚力，从而提出了一种创新的方法来实现可编程药物的递送。提出的技术方法不仅扩大了我们对HOF作为生物材料的理解，而且还具有对神经科学疾病的神经科学研究和治疗干预的潜力。除了其技术范围之外，该项目还通过“工程生物材料研究”（Bring）外展计划的计划纳入了更广泛的影响。该计划旨在参与奥斯汀社区学院（ACC）的代表性不足的工程专业学生，参与与生物材料研究有关的理论和实用模块。这项研究对推进我们对HOF作为生物材料的基本理解有深远的影响，从而影响了神经科学研究技术和神经系统疾病中治疗应用的发展。科学，技术，工程和数学（STEM）学生的参与，尤其是在ACC中的人数不足的学生，与更广泛的承诺相吻合，致力于促进科学社区的多样性和包容性。该奖项反映了NSF的法定任务，并通过使用该基金会的智力功能和广泛的影响来评估CRETERIA CREITERIA CRITERIA。