NCS-FO: Sub-millisecond Optically-triggered Compound Release to Study Real-time Brain Activity and Behavior

NCS-FO：亚毫秒光触发化合物释放，用于研究实时大脑活动和行为

• 批准号: 1631910
• 负责人: Zhenpeng Qin
• 金额: $ 80万
• 依托单位: University of Texas at Dallas
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1631910&HistoricalAwards=false
• 关键词: NCS; FO; Sub; millisecond; Optically

1631910Qin, ZhenpengUnderstanding how the brain controls behavior requires advanced tools to manipulate brain activity. Inspired by recent progress in optogenetics (i.e., a technique to control selected types of brain cells with genetic modification and light stimulation), this project seeks to develop a new set of tools that will allow localized and ultrafast control of brain activity to influence behavior in freely-moving animals. This will be achieved by using light stimulation to rapidly release compounds that are encapsulated in tiny nanometer-sized particles. The ultrafast feature of this novel compound technology is ideally suited to manipulate brain activity that typically occurs on the scale of milliseconds. Importantly, this new technology is suited to packaging and releasing a wide range of chemical and biological compounds, as well as combinations of such compounds. The project's success will have a number of broader impacts. Scientifically, this project will generate a new technology to better understand how the brain works, and thus new knowledge about the brain and behavior. The ultrafast compound release method can potentially develop into a platform technology for other research areas, including the nervous system outside the brain. The collaborative environment of this project will provide interdisciplinary training opportunities for two graduate students with cutting-edge technologies in the fields of engineering and neuroscience. Finally, this project will promote STEM education both in the lab and through community outreach programs. Advances in methodologies and tools for neuroscience research often lead to fundamental insights into the function of the central and periphery nervous system. Currently available methods for drug infusions using relatively large metal cannulas are not ideal for studies in freely behaving animals, because drug delivery is slow and the cannulas often destroy the brain area under study and/or overlying brain areas. New methods are needed to perform drug infusion or local release in a minimally invasively manner in freely moving animals. Inspired by recent developments in optogenetics, the PIs will develop a versatile optically-triggered system for sub-millisecond compound burst release for the real-time study of brain activity and behavior. Plasmonic liposomes, i.e. liposomes coated with a gold shell layer, can encapsulate a wide range of molecular compounds and be deposited locally in the brain. Due to the small width and poor clearance of the extracellular space in the brain, the plasmonic liposomes can be designed to stay in the injected area for prolonged periods of time. The encapsulated compound can then be quickly burst-released by a near-infrared pulsed laser via an implanted optical fiber. The encapsulated compounds can be designed to release by repeated triggers, allowing multiple on-demand drug release events over an extended period for behavioral studies. In this project, an integrated approach will be developed to deliver and release the encapsulated compounds, and to study the resulting brain activity and behavior change in real-time utilizing Pavlovian fear conditioning. Successful development of this sub-millisecond optically-triggered burst release technique will represent a major technological advancement that addresses the limitations of current techniques for behavioral research. Specifically, improved bio-compatibility and reduced invasiveness are anticipated by the by one-time nanoparticle infusion and on-demand light-triggered drug release. The fast release feature of the new technique will provide sufficient speed to study neuronal communication in neuroscience research. Furthermore, this technique will find wide applications in neuropharmacology research where targeted delivery and localized rapid release are currently unavailable.

1631910秦振鹏了解大脑如何控制行为需要先进的工具来操纵大脑活动。受光遗传学最新进展的启发（即，这是一种通过基因修饰和光刺激控制选定类型脑细胞的技术），该项目旨在开发一套新的工具，允许对大脑活动进行局部和超快速控制，以影响自由移动动物的行为。这将通过使用光刺激来快速释放封装在微小纳米尺寸颗粒中的化合物来实现。这种新型复合技术的超快特性非常适合操纵通常在毫秒级发生的大脑活动。重要的是，这项新技术适用于包装和释放各种化学和生物化合物，以及这些化合物的组合。该项目的成功将产生一些更广泛的影响。从科学上讲，这个项目将产生一种新的技术，以更好地了解大脑是如何工作的，从而了解大脑和行为的新知识。超快化合物释放方法有可能发展成为其他研究领域的平台技术，包括脑外神经系统。该项目的协作环境将为两名研究生提供跨学科培训机会，掌握工程和神经科学领域的尖端技术。最后，该项目将通过实验室和社区外展计划促进STEM教育。 神经科学研究方法和工具的进步往往导致对中枢和外周神经系统功能的基本见解。目前可用的使用相对较大的金属套管的药物输注方法对于在自由行为的动物中的研究并不理想，因为药物递送缓慢并且套管经常破坏研究中的脑区域和/或覆盖的脑区域。需要新的方法来在自由移动的动物中以微创方式进行药物输注或局部释放。受光遗传学最新发展的启发，PI将开发一种多功能的光学触发系统，用于亚毫秒化合物的爆发释放，用于大脑活动和行为的实时研究。等离子体脂质体，即涂覆有金壳层的脂质体，可以包封广泛的分子化合物并局部沉积在脑中。由于脑中细胞外空间的小宽度和差的清除率，等离子体脂质体可以被设计为在注射区域中停留延长的时间段。封装的化合物然后可以通过植入的光纤通过近红外脉冲激光快速爆发释放。包封的化合物可以被设计成通过重复触发来释放，从而允许在延长的时间段内进行多次按需药物释放事件以用于行为研究。在该项目中，将开发一种综合方法来递送和释放封装的化合物，并利用巴甫洛夫恐惧条件反射实时研究由此产生的大脑活动和行为变化。这种亚毫秒光触发爆发释放技术的成功开发将代表一个重大的技术进步，解决了目前的行为研究技术的局限性。具体而言，通过一次性纳米颗粒输注和按需光触发药物释放，预期生物相容性得到改善，侵入性降低。新技术的快速释放特性将为神经科学研究中的神经元通信研究提供足够的速度。此外，该技术将在神经药理学研究中找到广泛的应用，其中靶向递送和局部快速释放目前不可用。

项目成果

Ultrafast Pulsed Laser Induced Nanocrystal Transformation in Colloidal Plasmonic Vesicles

• DOI: 10.1002/adom.201800726
• 发表时间: 2018-09
• 期刊: Advanced Optical Materials
• 影响因子: 9
• 作者: M. Karim;Xiuying Li;P. Kang;J. Randrianalisoa;Dineli T. S. Ranathunga;S. Nielsen;Zhenpeng Qin;D. Qian

Understanding the Collective Optical Properties of Complex Plasmonic Vesicles

• DOI: 10.1002/adom.201700403
• 发表时间: 2017-10-16
• 期刊: ADVANCED OPTICAL MATERIALS
• 影响因子: 9
• 作者: Randrianalisoa, Jaona;Li, Xiuying;Qin, Zhenpeng
• 通讯作者: Qin, Zhenpeng

Rock the nucleus: significantly enhanced nuclear membrane permeability and gene transfection by plasmonic nanobubble induced nanomechanical transduction

• DOI: 10.1039/c7cc09613e
• 发表时间: 2018-03-11
• 期刊: CHEMICAL COMMUNICATIONS
• 影响因子: 4.9
• 作者: Li, Xiuying;Kang, Peiyuan;Qin, Zhenpeng
• 通讯作者: Qin, Zhenpeng

Near‐Infrared Light Triggered‐Release in Deep Brain Regions Using Ultra‐photosensitive Nanovesicles

使用超光敏纳米囊泡在大脑深部区域触发近红外光释放

• DOI: 10.1002/ange.201915296
• 发表时间: 2020
• 期刊: Angewandte Chemie
• 作者: Xiong, Hejian;Li, Xiuying;Kang, Peiyuan;Perish, John;Neuhaus, Frederik;Ploski, Jonathan E.;Kroener, Sven;Ogunyankin, Maria O.;Shin, Jeong Eun;Zasadzinski, Joseph A.
• 通讯作者: Zasadzinski, Joseph A.

Site-Selective Nucleation and Size Control of Gold Nanoparticle Photothermal Antennae on the Pore Structures of a Virus

• DOI: 10.1021/jacs.8b10446
• 发表时间: 2018-12-12
• 期刊: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
• 影响因子: 15
• 作者: Benjamin, Candace E.;Chen, Zhuo;Gassensmith, Jeremiah J.
• 通讯作者: Gassensmith, Jeremiah J.