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

职业：测量生命系统中氧化还原电位的定量纳米传感器

• 批准号: 1752506
• 负责人: Daniel Heller
• 金额: $ 50万
• 依托单位: Sloan Kettering Institute For Cancer Research
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-02-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1752506&HistoricalAwards=false
• 关键词: CAREER; Quantitative; Nanosensor; Measure; Redox; CAREER; Quantitative; Nanosensor; Measure; Redox

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.

在我们体内的细胞和组织中发生的氧化还原（氧化还原）反应对于它们的正常功能至关重要，并且对衰老和许多疾病（包括癌症）具有影响。许多疗法和食物具有抗氧化特性，但是研究人员对它们可能如何影响我们的细胞和身体有不完整的了解。该项目的目的是开发新的纳米技术，以改善细胞和生物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。 首席研究者的实验室正在通过研究具有独特特性的新材料来开发这些功能，这些材料可能会对许多领域产生重大影响。科学家，学生，企业家甚至艺术家都会共同努力，向公众传授这些材料，对它们进行新发现，并使他们比以往任何时候都有更多的人。在细胞代谢领域的越来越多的工作表明，许多基本生物学过程受到氧化还原化学的控制。氧化还原现象的变化也与包括癌症在内的许多疾病有关。但是，反应性物种在癌细胞信号传导和生存中的作用并不理解，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呈现癌症的基本代谢和能量异常，作为定义该疾病的新标志。尽管如此，对信号通路中遗传改变与代谢和生物能变化的复杂表型输出之间的连接的理解是粗略的。在生物学中进行氧化还原测量的当前选择均未达到该领域的独特需求。在不同实验室之间，对活组织中的氧化还原电位进行定量可以准确比较测量。对整个生理范围的细胞环境中的氧化还原电位敏感的工具将使研究人员获得更可检验的假设。许多领域，包括诊断，工艺工程，化学产品测试和安全性，药物筛查和药物开发也可能受益于测量或传输电化学信号的能力。在该项目中，PI将开发一类新的光学记者，以定量在活细胞和生物中测量全范围的氧化还原电位。该应用的总体目的是将光致发光碳纳米管的固有电压灵敏度和发射响应转化为生物系统。纳米管将采用新的共价和非共价功能化方法来调节纳米管发射，以针对整个生理范围的特定灵敏度进行设计。这种方法将开发新的功能，以了解和控制生物环境中纳米管的近红外光学响应，并调节这些材料的生物学相互作用以靶向特定的亚细胞隔室。这些传感器将用于在包括KRAS突变肿瘤在内的正常状态和患病状态下审查氧化还原景观。为了协助研究材料的开发和传播，并向公众传授有关这些新材料和发现的知识，将要实施一些计划。这位主要研究人员设计了一个生物工程研究项目，该项目将在以STEM宪章高中进行，以开发调节碳纳米管传感器的长期生物相容性的方法。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“纳米火山”来教育公众并提高纳米/生物科学/艺术社区的研究材料的可用性。将启动一项新的本科工程夏季计划，以使工程专业的学生在癌症研究环境中工作的经验，同时使教职员工和学员访问具有工程背景的学生。