US-Taiwan Planning Visit: Interrogating Nanodiamond-Cellular Interactions

这项提案的目标是汇集美国和台湾研究人员的专业知识，研究纳米金刚石，这种有前途的碳颗粒，已被证明可以显着提高分子成像和其他应用的安全性和效率，从根本上与生物系统相互作用。在生物工程、材料科学、化学和工程教育界以及许多其他领域，研究对新材料的基本生物反应的能力仍然是一个重要的需求。从这些研究中收集的信息可以为广泛的应用改进材料设计原则。这项工作将有助于合理设计和化学修饰独特的纳米金刚石表面，以实现更好的生物相容性，并深入了解细胞在暴露于这些物质后的反应。这项研究将对提高纳米金刚石的安全性和广泛应用产生广泛的影响。该项目的一个主要部分是开发新颖的K-12教材，特别是纳米钻石主题的漫画书。图形材料是促进学生学习复杂主题的好方法，并将有助于激励新一代探索科学和工程领域的未来职业。具体来说，加州大学洛杉矶分校的研究生和学术协调员团队将与台湾合作者合作，创造纳米钻石诺拉和尼尔的故事情节。诺拉和尼尔将作为这本书的主角，这本书将重点介绍他们从充当发动机磨料到作为探险家进入细胞的故事。诺拉和尼尔将在旅途中得到年轻科学家的指导。纳米金刚石已成为基础生物学研究中很有前途的材料。截短的八面体纳米金刚石表面的多面性导致其独特的物理化学性质，从而显著提高分子显像剂的有效性和安全性。这些特性包括协调水的能力，这是优化成像对比度的关键要求。因此，与所有纳米颗粒化合物相比，基于纳米金刚石的成像具有独特的最高效率。考虑到纳米金刚石作为纳米标记材料的前景，更好地理解纳米金刚石与细胞相互作用的机制变得越来越重要。这项工作旨在汇集一组合作者，提供迄今为止最全面的研究，研究广泛类别的纳米金刚石（胺，羧基功能化，荧光/N-V中心等）如何与细胞相互作用。诸如半胱天冬酶测定、定量实时聚合酶链反应、活力测定和乳酸脱氢酶测定等方法将被实施，为颗粒暴露的生物反应提供新的基本机制见解。此外，CyTOF，一个强大的单细胞研究平台，可以进行多途径相互作用分析，将提供迄今为止最详细的关于细胞信号成分串扰如何共同控制细胞行为的观点。这项工作将在技术上培训未来的科学和工程领导者方面发挥重要作用。

The goal of this proposal is to bring together expertise from researchers in the US and Taiwan to study how nanodiamonds, promising carbon particles that have been shown to markedly improve the safety and efficiency of molecular imaging and other applications, fundamentally interact with biological systems. The ability to examine the basic biological response to novel materials remains an important need in the bioengineering, materials science, chemistry and engineering education communities, among many others. The information gleaned from these studies can improve materials design principles for a broad array of applications. This work will enable rational design and chemical modification of the unique nanodiamond surfaces to realize improved biocompatibility and insight into how cells respond following exposure to these agents. This study will result in broad impact upon improving the safety and thus widespread implementation of nanodiamonds.A major part of this project is developing novel K-12 teaching materials, specifically a nanodiamond-themed comic book. Graphic materials are a great way to facilitate student learning of complex topics, and will help inspire a new generation to explore future careers in science and engineering. Specifically, a team of graduate students and the academic coordinator of UCLA will partner with Taiwanese collaborators to create the Nanodiamond Nora and Neal storyline. The Nanodiamond Nora and Neal will serve as the main characters of the book which will highlight their story from serving as engine abrasives to journeying into cells as explorers. Nora and Neal will be mentored by young scientists during the course of their journey. Technical AbstractNanodiamonds have emerged as promising materials for fundamental biological investigations. The faceted nature of the truncated octahedral nanodiamond surfaces results in unique physical-chemical properties that mediate marked improvements in the efficacy and safety of molecular imaging agents. These properties include the ability to coordinate water, a key requirement for optimizing imaging contrast. As such, nanodiamond-based imaging has uniquely resulted in among the highest efficiencies compared to all nanoparticle compounds. Given their promise as nano-labeling materials, it is becoming increasingly important to better understand the mechanisms that underlie nanodiamond-cell interactions. This work aims to bring together a team of collaborators to provide the most comprehensive study to date of how broad classes of nanodiamonds (amine, carboxyl-functionalized, fluorescent/N-V center, etc.) interact with cells. Methodologies such as caspase assays, quantitative real-time polymerase chain reaction, viability assays, and lactate dehydrogenase assays will be implemented to provide new fundamental mechanistic insight into the biological response to particle exposure. Furthermore, CyTOF, a powerful single cell investigation platform that enables multi-pathway interaction assays will provide the most elaborate view to date of how cell signaling components crosstalk to collectively govern cell behavior. This work will play a major role in technically training future scientific and engineering leaders.