CAREER: A Quantitative Nanosensor to Measure Redox Potential in Living Systems

氧化还原反应发生在我们身体的细胞和组织中，对它们的正常功能是必不可少的，并与衰老和包括癌症在内的许多疾病有关。许多疗法和食物都有抗氧化特性，但研究人员对它们可能如何影响我们的细胞和身体还没有完全了解。该项目的目的是开发新的纳米技术，以改进对细胞和生物体中氧化还原现象的测量，以更好地了解它们与健康和疾病的关系。首席研究员的实验室正在通过研究具有独特性能的新材料来开发这些能力，这些材料可能会对许多领域产生重大影响。科学家、学生、企业家，甚至艺术家将共同努力，向公众传授这些材料，做出关于它们的新发现，并使更多的人比以往任何时候都能使用它们。越来越多的细胞代谢领域的研究表明，许多基本的生物过程是在氧化还原化学的控制下进行的。氧化还原现象的变化也与包括癌症在内的许多疾病有关。然而，活性物质在癌细胞信号传递和生存中的作用还不是很清楚，包括促氧化剂和抗氧化剂的作用。一项巨大的努力已经开始，将癌症的基本代谢和能量异常作为定义这种疾病的新标志。尽管如此，对信号通路中的遗传变化与由此产生的代谢和生物能量变化的复杂表型输出之间的联系的理解仍然很粗略。目前在生物学中进行氧化还原测量的选择不能满足该领域的独特需求。生物组织中氧化还原电势的量化将允许在不同实验室之间准确地比较测量结果。一种对细胞环境中更广泛的生理范围内的氧化还原电位敏感的工具将给研究人员提供更多可验证的假说。许多领域，包括诊断、过程工程、化学产品测试和安全、药物筛选和药物开发，也可以受益于光学测量或传输电化学信号的能力。在这个项目中，PI将开发一种新的光学记录器来定量测量活细胞和生物体的全范围氧化还原电位。这一应用的总体目标是将光致发光碳纳米管广泛的本征电压灵敏度和发射响应转化为生物系统。利用新的共价和非共价功能化方法来调节纳米管的发射，纳米管将被设计成在生理范围内具有特定的灵敏度。这种方法将开发新的能力，以了解和控制生物环境中纳米管的近红外光学响应，以及调节这些材料的生物相互作用，以针对特定的亚细胞室。这些传感器将被用来询问正常和疾病状态下的氧化还原景观，包括Kras突变肿瘤。为了协助编写和传播研究材料，并利用这些新材料和研究结果向公众传授知识，将实施几项倡议。首席研究员设计了一个生物工程研究项目，将在一所以STEM为重点的特许高中进行，以开发调节碳纳米管传感器长期生物兼容性的方法。首席研究人员还与一位常驻艺术家合作，使用基于碳纳米管的“纳米颜料”来教育公众，并为纳米/生物科学/艺术社区改善研究材料的可用性。将启动一项新的本科工程暑期计划，为工程学学生提供在癌症研究环境中工作的经验，同时让教职员工和实习生接触具有工程背景的学生。

The oxidation-reduction (redox) reactions occurring in the cells and tissues of our body are essential to their proper function and have implications in aging and many diseases, including cancer. Many therapies and foods have anti-oxidant properties, but researchers have an incomplete understanding of how they might affect our cells and bodies. The aim of the project is to develop new nanotechnologies to improve the measurement of redox phenomena in cells and organisms to give a better picture of how they relate to health and disease. The principal investigator's laboratory is developing these capabilities by studying new materials with unique properties that may have big impact on many fields. Scientists, students, entrepreneurs, and even artists will work together to teach the public about these materials, make new discoveries about them, and to make them available to more people than ever before. A growing body of work in the field of cellular metabolism has shown that many fundamental biological processes are under the control of redox chemistry. Changes in redox phenomena are also implicated in many diseases, including cancer. The role of reactive species in cancer cell signaling and survival is not well-understood, however, including the roles of pro- and anti-oxidants. A large effort has started to present the basic metabolic and energetic abnormalities of cancer as a new hallmark which defines the disease. Still, the understanding of the connections between the genetic alterations in signaling pathways and the resulting complex phenotypic output of metabolism and bioenergetic changes is cursory. Current options for making redox measurements in biology fall short of the unique needs of the field. The quantification of redox potentials in living tissues would allow for measurements to be compared accurately between different laboratories. A tool sensitive to redox potentials in the cellular environment across the wider physiologic range would give researchers access to more testable hypothesis. Many fields, including diagnostics, process engineering, chemical product testing and safety, drug screening, and drug development could also benefit from the ability to measure or transmit electrochemical signals optically. In this project, the PI will develop a new class of optical reporters to measure the full-range redox potential quantitatively in live cells and organisms. The overall objective of this application is to translate the wide intrinsic voltage sensitivity and emission response of photoluminescent carbon nanotubes into biological systems. Nanotubes will be engineered for specific sensitivity across the physiologic range using new covalent and non-covalent functionalization methods to modulate nanotube emission. This approach will develop new capabilities to understand and control the near-infrared optical response of nanotubes within biological environments, as well as to modulate biological interactions of these materials to target specific sub-cellular compartments. These sensors will be used to interrogate redox landscapes in normal and diseased states, including Kras-mutant tumors. To assist with the development and dissemination of the research materials, and to teach the public about these new materials and findings with them, several initiatives are going to be implemented. The principal investigator designed a bioengineering research project to be conducted in a STEM-focused charter high school to develop methods to modulate the long-term biocompatibility of carbon nanotube sensors. The principal investigator is also working with a resident artist to use carbon nanotube-based 'nanopaints' to both educate the public and improve the availability of research materials for the nano/bioscience/art communities. A new undergraduate engineering summer program will be initiated to give engineering students the experience of working in a cancer research setting while giving faculty and trainees access to students with engineering backgrounds.