Nonobiosensors for Probing Chemical Exposure and Metabolism Pathways of Individua

描述(申请人提供)：虽然许多化学品的毒性性质，如致癌物质，已经进入环境是众所周知的，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。迫切需要开发一种分子工具，能够在化学暴露后监测生化过程或检测活细胞中的特定生物标记物。从根本上说，对单个完整细胞内的细胞信号通路进行微创分析正变得越来越重要，因为一个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和开发纳米生物传感器，以探测化学物质暴露和个体活细胞的健康影响。这项拟议的技术可以提供对完整细胞功能的前所未有的见解，使在功能细胞架构的背景下研究分子功能成为可能。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)和暴露的相关生物标志物苯并[a]芘(BPT)的纳米传感器；2)开发纳米生物传感器的双靶点传感技术，利用相分辨检测实现BaP和BPT的同时检测；3)研究暴露于BaP的单个活细胞中的暴露和代谢途径。该项目将开发的纳米探针将为生物技术、分子生物学和环境卫生研究、原位细胞内信号过程的研究以及化学传输和毒性的研究开辟新的应用领域。

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.