Mechanoluminescent nanomaterials for optogenetic neuromodulation

神经系统疾病/障碍的患病率呈指数级激增，部分原因是 老年人口对认知障碍的预防和治疗构成了重大挑战， 感觉和运动功能。然而，我们对这一现象背后的机制认识不足 许多神经系统疾病的发病机制延迟了有效治疗方法的发展。 挑战。光遗传学的最新进展为研究复杂的神经电路和 大脑功能。然而，由于光子的穿透深度有限，光源对 活体动物的脑组织控制光敏离子通道一直是最大的挑战之一。 光遗传学。在这方面，我们的目标是开发一种模块化的机械发光(ML)材料平台 无创的、声激活的各种光遗传通道用于神经调制，具有高度的 时空分辨率。这个项目建立在我们最近的技术成就的基础上，在这些成就中，我们 开发了各种合成方法来制备新型结构的无机纳米材料和高性能材料 压电有机纳米纤维碎片。基于我们的初步计算模型，我们假设 这种结构使更有效的菌株能够最大限度地提高无机-有机材料的ML性能 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来控制 并研究了纳米颗粒的形貌和尺寸对ML性能的影响。 此外，这些纳米颗粒与包裹聚合物之间的相互作用将得到优化，以 最大限度地提高纳米复合材料的ML性能。在目标2中，我们将表征材料的压电性 电纺纤维衍生纳米膜并研究ML纳米颗粒的掺入 用于提高ML性能的压电纳米片。一种基于神经干细胞系的体外模型 用通道视紫红质-2转导的将被用来确定这些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纳米粒子提供材料基础 可注射到循环系统(目标1)和可注射到感兴趣部位的ML纳米膜(目标2)。 这一探索性项目的结果有望确定ML纳米材料平台的候选者 在后续研究中进行进一步的优化和动物试验。

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.