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 Qin，Zhenpengundersanderdandersand，脑控制行为的方式需要高级工具来操纵大脑活动。受到光遗传学最近进展的启发（即，一种以遗传修饰和光刺激来控制选定的脑细胞类型的技术），该项目旨在开发一组新的工具，这些工具将允许对脑活动的局部和超快控制以影响自由动物的行为。这将通过使用光刺激来快速释放封装在微小纳米大小的颗粒中的化合物来实现。这种新型复合技术的超快特征非常适合操纵通常在毫秒尺度上发生的大脑活动。重要的是，这项新技术适合包装和释放多种化学和生物学化合物以及此类化​​合物的组合。该项目的成功将产生许多更广泛的影响。从科学上讲，该项目将生成一项新技术，以更好地了解大脑的工作原理，从而了解大脑和行为的新知识。超快复合释放方法可能会发展为其他研究领域的平台技术，包括大脑外的神经系统。该项目的协作环境将为两位研究生提供工程和神经科学领域的尖端技术，为两名研究生提供跨学科的培训机会。最后，该项目将在实验室和社区外展计划中促进STEM教育。 神经科学研究方法和工具的进步通常会导致对中央和周围神经系统功能的基本见解。目前使用相对较大的金属插管的药物输注方法可用的方法并不理想地研究自由行为的动物，因为药物输送缓慢，并且插管经常破坏正在研究和/或上覆盖大脑区域的大脑区域。需要新的方法以自由移动的动物以微创的方式进行药物输注或局部释放。受到光遗传学的最新发展的启发，PI将开发一种多功能光学触发的系统，用于用于实时研究大脑活动和行为的亚毫秒复合爆发。等离子脂质体，即涂有金壳层的脂质体，可以封装多种分子化合物，并局部沉积在大脑中。由于大脑中细胞外空间的宽度和较差的间隙较小，因此可以设计等离子脂质体的血浆脂质体长时间留在注射区域。然后，可以通过植入的光纤通过近红外脉冲激光器快速爆发封装的化合物。封装的化合物可以通过重复的触发器释放，从而在行为研究的长时间内允许多次按需药物释放事件。在该项目中，将开发一种综合方法来传递和释放封装的化合物，并研究实时利用帕夫洛夫恐惧调节的实时大脑活动和行为变化。成功开发了这一亚毫秒的光学触发爆发技术将代表一个主要的技术进步，该技术可以解决当前技术研究的局限性。具体而言，通过一次性纳米颗粒输注和点播光触发的药物释放，预计生物兼容和侵袭性降低。新技术的快速发布功能将提供足够的速度来研究神经科学研究中的神经元通信。此外，该技术将在神经药理研究中找到广泛的应用，目前无法使用有针对性的交付和局部快速释放。

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

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.

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

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.