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： 长期以来一直需要监测神经元活动中化学信号传导的技术 了解大脑的神秘功能，并解散 神经系统疾病，例如癫痫和阿尔茨海默氏病。这个项目创造了小说生物 - 用于物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，例如乙酰胆碱。 K+，Na+，Cl-和Ca2+等生理离子是 神经元的膜潜力的关键以及作用电位的传播。体外和 在神经元交流过程中，这些离子水平的体内记录一直是 数十年来的研究。神经递质乙酰胆碱（ACH）参与记忆和 学习对阿尔茨海默氏病和精神疾病的影响。研究ACH是 对于阐明神经退行性的病理生理和理解 肠道微生物组与大脑健康之间的联系。提出的工作范围 申请有可能通过更好 了解疾病病理生理学。 该提案的直接目标是用双重创建生物正交的富富纳米传感器 功能。感知离子神经递质并在光线下释放这些化合物 刺激。纳米颗粒将使用荧光材料开发。荧光化合物 （氟原子含量较高的分子）极其非极性，不可偏振 它们与水和脂肪物质无法混乱的程度。也就是说，氟 化合物既是疏水和脂肪症。事实上，生活系统是 水和亲脂化合物，制造氟化碳生物正交，这意味着它们会做 不会因生物学打断。此功能允许开发稳定和无毒的纳米传感器 具有宽度应用程序。该提议回答的科学问题是（i）可以 我们控制荧光水接口，并使用部分氟化的电压敏感染料 为了无线接触的界面潜力读数？ （ii）我们可以在神经元中记录化学信号 使用平台和模块化荧光纳米传感器进行通信？ （iii）我们可以捕获氟吗 超疏水纳米颗粒中的亚固电压 - 酸，并使用蓝光进行局部释放 离子部分？ （iv）我们可以使用局部释放离子与神经细胞开始对话，并且 模仿化学信号？