Mechanoluminescent nanomaterials for optogenetic neuromodulation

用于光遗传学神经调节的机械发光纳米材料

• 批准号: 10616188
• 负责人: Jin Nam
• 金额: $ 28.24万
• 依托单位: UNIVERSITY OF CALIFORNIA RIVERSIDE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10616188
• 关键词: Achievement; Acoustics; Address; Animal Testing; Animals; BRAIN initiative; Biomedical Engineering; Brain; Cardiovascular system; Cations; Cell Line; Cognitive; Colloids; Complex; Computer Models; Data; Dependence; Development; Dimensions; Disease; Dissection; Electrospinning; Encapsulated; Engineering; Exhibits; Fiber; Fluorides; Goals; Growth; Health; Human; Hybrids; Impairment; In Situ; In Vitro; Injectable; Ion Channel; Ions; Light; Longitudinal Studies; Metals; Methods; Mission; Morphology; Motor; Nanostructures; Nervous System; Neurons; Neurophysiology - biologic function; Neurosciences Research; Pathogenesis; Pathologic; Penetration; Performance; Personal Satisfaction; Phase; Photons; Physiological; Physiology; Polymers; Prevalence; Prevention; Process; Property; Public Health; Research; Resolution; Sensory; Shapes; Signal Transduction; Site; Source; Structure; System; Technology; Testing; Therapeutic Intervention; Tissues; Transducers; United States National Institutes of Health; Yin; aging population; base; brain tissue; candidate identification; effective therapy; electrical potential; improved; in vitro Model; innovative technologies; interest; light emission; magnetic field; nanocomposite; nanofiber; nanomaterials; nanoparticle; nanopolymer; nerve stem cell; nervous system disorder; neural; neural circuit; neuroregulation; new technology; novel; novel therapeutic intervention; optogenetics; particle; polyvinylidene fluoride; rapid growth; response; spatiotemporal; therapeutic development; tool; transmission process; ultrasound; vinyl fluoride; wireless; zinc sulfide

The exponential surge in the prevalence of neurological diseases/disorders, partly due to the rapid growth in the aged population, poses a significant challenge to the prevention and treatment of impairments in cognitive, sensory, and motor functions. However, our insufficient understanding of the mechanisms underlying the pathogenesis of many neurological diseases delays the development of effective treatments to address this challenge. Recent advances in optogenetics have provided novel tools to investigate complex neural circuits and brain functions. Due to a limited penetration depth of photons, however, the invasiveness of light sources into the brain tissue of live animals to control opto-sensitive ion channels has been one of the major challenges in optogenetics. In this regard, our goal is to develop a modular mechanoluminescent (ML) material platform for the non-invasive, acoustic activation of various optogenetic channels for neural modulation with a high spatiotemporal resolution. This project builds upon our recent technological achievements, in which we developed various synthesis methods to produce novel structures of inorganic nanomaterials and high piezoelectric organic nanofiber fragments. Based on our preliminary computational modeling, we hypothesize that such structures enable greater effective strains that maximize the ML performance of the inorganic-organic hybrid nanomaterials. This project aims to develop two unique optogenetic modulation systems based on ML nanomaterials. In Aim 1, we will synthesize zinc sulfide nanoparticles doped with various metal ions to control emission wavelengths and investigate the effect of nanoparticle morphology and dimension on ML performance. Furthermore, the interaction between those nanoparticles and encapsulating polymer will be optimized to maximize the ML performance of nanocomposites. In Aim 2, we will characterize the piezoelectric properties of electrospun fiber-derived nanofragments and investigate the incorporation of ML nanoparticles into the piezoelectric nanofragments to boost ML performance. An in vitro model based on a neural stem cell line transduced with Channelrhodopsin-2 will be utilized to determine the performance of these ML nanomaterials for neuromodulation. Overall, we anticipate that these studies will provide material bases for ML nanoparticles injectable into the circulatory system (Aim 1) and for ML nanofragments injectable into a site of interest (Aim 2). The results of this exploratory project are expected to identify candidates for ML nanomaterial platforms for further optimization and animal testing in subsequent studies.

神经系统疾病/紊乱的发病率呈指数级激增，部分原因是 老年人口，对预防和治疗认知障碍提出了重大挑战， 感觉和运动功能。然而，我们对这种现象的机制了解不够 许多神经系统疾病的发病机制延迟了有效治疗方法的开发 挑战.光遗传学的最新进展为研究复杂的神经回路提供了新的工具， 大脑功能然而，由于光子的穿透深度有限，光源对光子的侵入性受到限制。 活体动物的脑组织来控制光敏感离子通道一直是 光遗传学在这方面，我们的目标是开发一个模块化的机械发光（ML）材料平台， 非侵入性的，声学激活各种光遗传学通道用于神经调制， 时空分辨率该项目建立在我们最近的技术成就之上，其中我们 开发了各种合成方法，以生产新型结构的无机纳米材料和高 压电有机陶瓷碎片。基于我们初步的计算模型，我们假设 这种结构能够实现更有效的菌株，使无机-有机组合物的ML性能最大化， 杂化纳米材料本项目旨在开发两种独特的基于ML的光遗传学调制系统 纳米材料在目标1中，我们将合成掺杂各种金属离子的硫化锌纳米颗粒，以控制 发射波长，并研究纳米颗粒形态和尺寸对ML性能的影响。 此外，这些纳米颗粒和包封聚合物之间的相互作用将被优化， 最大化纳米复合材料的ML性能。在目标2中，我们将表征 电纺纤维衍生的纳米片段，并研究ML纳米颗粒掺入到 压电纳米碎片，以提高ML性能。基于神经干细胞系的体外模型 将利用用视紫红质-2转导的细胞来确定这些ML纳米材料的性能 用于神经调节。总的来说，我们预计这些研究将为ML纳米颗粒提供材料基础 可注射到循环系统中（目的1）和ML纳米片段可注射到感兴趣的部位（目的2）。 这个探索性项目的结果预计将确定ML纳米材料平台的候选者， 在后续研究中进一步优化和动物试验。