Nonobiosensors for Probing Chemical Exposure and Metabolism Pathways of Individua

描述（由申请人提供）：虽然许多化学品（如致癌物质）的毒性性质已被广泛了解，但这些化学品在细胞和分子水平上发挥毒性作用的机制现在才开始被理解。迫切需要开发一种能够监测生物化学过程或检测化学暴露后活细胞中特定生物标志物的分子工具。单个完整细胞内细胞信号通路的微创分析从根本上变得越来越重要，因为群体中的细胞对外部刺激的反应是异步的。这项研究的目的是进行基础研究，并开发纳米生物传感器，用于探测单个活细胞的化学暴露和健康影响。所提出的技术可以提供前所未有的完整细胞功能的见解，允许在功能细胞结构的背景下研究分子功能。这项拟议的研究将有助于生物学和医学的未来进步，这与国家环境健康科学研究所（NIEHS）的使命直接相关。该项目的具体目标是：1）开发用于监测致癌化合物苯并[a]芘（BaP）和相关暴露生物标志物苯并芘四醇（BPT）的纳米传感器; 2）开发纳米生物传感器的双靶传感技术，以实现使用相分辨检测同时检测BaP和BPT;以及3）研究暴露于BaP的单个活细胞中的暴露和代谢途径。该项目开发的纳米探针将为生物技术、分子生物学和环境健康研究、原位细胞内信号传导过程的研究以及化学运输和毒性的调查等领域的大量应用开辟新的视野。

DESCRIPTION (provided by applicant): Although the toxic nature of many chemicals, such as carcinogenic species, which have found their way into the environment is well-known, the mechanisms by which these chemicals exert their toxic effects at the cellular and molecular level are only now beginning to be understood. There is a strong need for developing a molecular tool that is capable of monitoring biochemical processes or detecting specific biomarkers in a living cell following chemical exposure. Minimally invasive analysis of cellular signaling pathways inside single intact cells is becoming increasingly important fundamentally because cells in a population respond asynchronously to external stimuli. The objective of this research is to conduct fundamental research and develop nanobiosensors for probing chemical exposure and health effects of individual living cells. The proposed technique could provide unprecedented insights into intact cell function, allowing studies of molecular functions in the context of the functional cell architecture. This proposed research will contribute to future advancements in biology and medicine, which is directly relevant to the mission of National Institute of Environmental Health Sciences (NIEHS). The specific aims of the project are: 1) Develop a nanosensor for monitoring the carcinogenic compound, benzo[a]pyrene (BaP) and the related biomarker of exposure, benzopyrene tetrol (BPT), 2) Develop dual-target sensing technology for the nanobiosensor to achieve simultaneous detection of BaP and BPT using phase-resolved detection, and 3) Investigation of exposure and metabolism pathways in a single living cell exposed to BaP. The nanoprobes to be developed in this project will open new horizons to a host of applications in biotechnology, molecular biology and environmental health research, and the study of in situ intracellular signaling processes, and investigations of the chemical transport and toxicity.