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?

项目总结： 长期以来，人们一直希望使用监测神经元活动中的化学信号的技术。 为了了解大脑的神秘功能，以及揭开 神经性疾病，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体内外成像的正交型纳米传感器 神经递质，如乙酰胆碱。K+、Na+、Cl-、Ca2+等生理离子 神经元膜电位和动作电位传播的关键。体外和体外- 在神经元通讯过程中活体记录这些离子的水平一直是 几十年来的研究。神经递质乙酰胆碱(ACh)参与记忆和 学习与阿尔茨海默病和精神障碍的关系。学习ACH是 对于揭开神经退行性变的病理生理学和深入研究 肠道微生物群和大脑健康之间的联系。本文件中提议的工作范围 应用程序有可能通过更好的 了解疾病的病理生理学。 这项提议的直接目标是创建具有双重结构的生物正交氟纳米传感器 功能。感受离子神经递质，并在光线下释放这些化合物 刺激。这种纳米粒子将使用含氟材料进行开发。含氟化合物 (氟原子含量高的分子)是极非极性和非极化的 它们与水和脂肪物质不相容的程度。也就是说，氟化 化合物既是疏水的，又是疏油的。事实上，生命系统是由 水和亲脂化合物，使氟碳化合物具有生物正交性，这意味着它们确实 而不是干扰生物学。这一特征使稳定和无毒的纳米传感器得以开发 有着广泛的应用。这项提议回答的科学问题是：(I)可以 我们控制氟-水界面，并使用部分氟化的压敏染料 用于非接触式界面电势读数？(Ii)我们能记录神经元中的化学信号吗？ 使用平台和模块化氟纳米传感器进行通信？(Iii)我们能捕获氟化物吗？ 超疏水纳米粒中的亚稳态光酸，并使用蓝光局部释放 离子部分？(四)能否通过局部释放离子与神经细胞展开对话，以及 模仿化学信号？