Building a two-way communication system: Bio-orthogonal superhydrophobic nanoparticles for controlled stimulation and real-time sensing of neurotransmitters

构建双向通信系统：生物正交超疏水纳米颗粒用于神经递质的受控刺激和实时传感

• 批准号: 10473375
• 负责人: Maral Mousavi
• 金额: $ 134.48万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-15 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10473375
• 关键词: Acetylcholine; Acids; Action Potentials; Affect; Alzheimer' s Disease; American; Biology; Brain; Chemicals; Communication; Development; Disease; Epilepsy; Fluorine; Fluorocarbons; Functional Imaging; Functional disorder; Goals; Hydrophobicity; In Vitro; Ions; Knowledge; Learning; Light; Membrane Potentials; Memory; Mental disorders; Mission; Monitor; Nerve Degeneration; Neurodegenerative Disorders; Neurons; Neurotransmitters; Organism; Physiological; Public Health; Research; Research Personnel; Signal Transduction; System; Technology; Time; United States National Institutes of Health; Water; Work; aqueous; brain health; gut microbiome; in vivo; in vivo imaging; interfacial; lipophilicity; lipophobicity; nanoparticle; nanosensors; nervous system disorder; neurotransmission; novel; small molecule; tool; voltage sensitive dye

Project Summary: Technologies for monitoring chemical signaling in neuronal activities have long been desired to understand the mysterious function of the brain, and the unravel underlying mechanisms of neurological disorders such as epilepsy and Alzheimer’s disease. This project creates novel bio- orthogonal nanosensors for in-vitro and in-vivo imaging of physiological ions and small molecule neurotransmitters such as acetylcholine. Physiological ions such as K+, Na+, Cl-, and Ca2+ are key to membrane potential of the neuron, and propagation of action potentials. In-vitro and in- vivo recording of levels of these ions during neuronal communication has been focus of research for decades. The neurotransmitter acetylcholine (ACh) is involved in memory and learning with implications in Alzheimer’s disease and psychiatric disorders. Studying ACh is important for unravelling the pathophysiology of neurodegenerative and understudying the connection between the gut microbiome and brain health. The scope of work proposed in this application has potential to contribute major advances in public health through better understanding of disease pathophysiology. The immediate goal of this proposal to create bio-orthogonal fluorous nanosensors with dual functionalities. To sense ionic neurotransmitters and to release these compounds upon light stimulation. The nanoparticles will be developed using fluorous materials. Fluorous compounds (molecules with high content of fluorine atoms) are extremely non-polar and non-polarizable to the extent that they are not miscible with water and fatty substances. That is, fluorinated compounds are both hydrophobic and lipophobic. As a matter of fact, living systems are made of water and lipophilic compounds, making fluorocarbons bio-orthogonal, meaning that they do not interfere with biology. This feature allows development of stable and nontoxic nanosensors with widespread applications. The scientific questions that this proposal is answering are (i) Can we control the fluorous- aqueous interface and use partially fluorinated voltage sensitive dyes for contact-free readout of interfacial potential? (ii) Can we record chemical signaling in neuronal communication using a platform and modular fluorous nanosensor? (iii) Can we trap fluorinated metastable-photo-acids in superhydrophobic nanoparticles and use blue light for local release of ionic moieties? (iv) Can we use local release of ions to start a dialogue with nerve cells, and mimic the chemical signaling?

项目摘要： 用于监测神经元活动中的化学信号传导的技术长期以来一直是期望的 了解大脑的神秘功能，并解开大脑的潜在机制， 神经系统疾病，如癫痫和阿尔茨海默病。该项目创造了新的生物- 用于生理离子和小分子的体外和体内成像的正交纳米传感器 神经递质如乙酰胆碱。生理离子如K+、Na+、Cl-和Ca 2+， 神经元膜电位和动作电位传播的关键。体外和体内- 在神经元通信期间这些离子的水平的体内记录已经成为 几十年的研究。神经递质乙酰胆碱（ACh）参与记忆， 学习与阿尔茨海默病和精神疾病的关系。研究ACh是 重要的是解开神经退行性疾病的病理生理学和了解 肠道微生物组和大脑健康之间的联系。本报告中提出的工作范围 应用有可能通过更好地促进公共卫生的重大进步， 了解疾病的病理生理学。 该提案的直接目标是创建具有双功能的生物正交氟纳米传感器， 功能。感知离子神经递质并在光照下释放这些化合物 刺激.纳米粒子将使用氟材料开发。含氟化合物 （具有高含量氟原子的分子）是极非极性的和不可极化的， 它们不与水和脂肪物质混溶的程度。也就是说，氟化 化合物既疏水又疏脂。事实上，生命系统是由 水和亲脂性化合物，使碳氟化合物生物正交，这意味着它们 不影响生物学。这一特性允许开发稳定和无毒的纳米传感器 具有广泛的应用。这个建议所回答的科学问题是：（i）能否 我们控制氟-水界面并使用部分氟化的电压敏感染料 用于界面电位的非接触读出？(ii)我们能否记录神经元中的化学信号 使用平台和模块化氟纳米传感器进行通信？(iii)我们能捕获氟化的 亚稳态光酸在超疏水纳米粒子和使用蓝光的局部释放 离子部分？(iv)我们能否利用局部释放的离子来启动与神经细胞的对话， 模仿化学信号