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/疾病患病率的指数激增，部分是由于 老年人口，对预防和治疗认知障碍的构成重大挑战， 感觉和运动功能。但是，我们对基于的机制的理解不足 许多神经系统疾病的发病机理延迟了有效治疗的发展来解决这一问题 挑战。光遗传学的最新进展提供了研究复杂的神经回路和 大脑功能。但是，由于光子的渗透深度有限，光源的侵入性 活动物的脑组织控制光敏感的离子通道一直是 光遗传学。在这方面，我们的目标是开发一个模块化机械发光（ML）材料平台 各种光遗传通道的非侵入性，声学激活，用于神经调节 时空分辨率。这个项目以我们最近的技术成就为基础 开发了各种综合方法，以生成无机纳米材料的新结构和较高的结构 压电有机纳米纤维碎片。根据我们的初步计算建模，我们假设 这样的结构可以使更大的有效菌株最大化无机有机的ML性能 混合纳米材料。该项目旨在开发基于ML的两个独特的光遗传学调制系统 纳米材料。在AIM 1中，我们将合成用各种金属离子掺杂的硫化锌纳米颗粒 发射波长并研究纳米颗粒形态和维度对ML性能的影响。 此外，这些纳米颗粒与封装聚合物之间的相互作用将被优化为 最大化纳米复合材料的ML性能。在AIM 2中，我们将表征的压电特性 电纺纤维衍生的纳米碎片，并研究将ML纳米颗粒掺入 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 将使用通道Ropopsin-2传递来确定这些ML纳米材料的性能 用于神经调节。总体而言，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（AIM 1）和ML纳米碎片中的注射到感兴趣的部位（AIM 2）。 预计该探索项目的结果将确定ML纳米材料平台的候选者 在随后的研究中进一步优化和动物测试。