Novel Hydrocyanine Probes for the Accurate Detection of Reactive Oxygen Species

用于准确检测活性氧的新型氢氰探针

• 批准号: 8647969
• 负责人: Jon P Anderson
• 金额: $ 21.29万
• 依托单位: LI-COR BIOSCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2016-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8647969
• 关键词: Alzheimer' s Disease; Animals; Antioxidants; Area; Arteriosclerosis; Arthritis; Atherosclerosis; Back; Behavioral Research; Biocompatible Materials; Biological; Biology; Biomedical Research; Blood; Cell Culture Techniques; Cell physiology; Cells; Chemicals; Clinical; Detection; Development; Diabetes Mellitus; Diabetic Retinopathy; Diagnosis; Diagnostic; Disease; Dyes; Effectiveness; Environment; Family; Flow Cytometry; Fluorescence; Funding Opportunities; Goals; Image; In Vitro; Investigation; Laboratory Research; Life; Link; Malignant Neoplasms; Marketing; Medicine; Microscopy; Monitor; Myocardial Infarction; Optics; Organic solvent product; Paper; Parkinson Disease; Performance; Pharmaceutical Preparations; Phase; Physiological Processes; Play; Positioning Attribute; Preclinical Drug Evaluation; Principal Investigator; Process; Property; Publications; Reactive Oxygen Species; Reader; Reporting; Research; Research Personnel; Role; Sampling; Signal Pathway; Signal Transduction; Small Business Innovation Research Grant; Solubility; Specificity; Specimen; Staging; System; Technology; Testing; Time; Tissue Sample; Water; Work; biomedical scientist; clinical application; cyanine; cyanine dye; design; flexibility; high throughput screening; human disease; imaging probe; improved; in vivo; in vivo imaging; innovation; interest; next generation; novel; novel strategies; oxidation; public health relevance; ratiometric; screening; theories; tool; tumor progression; water solubility

DESCRIPTION (provided by applicant): Reactive oxygen species (ROS) are involved in numerous cell-signaling pathways. They have been implicated in over 150 diseases including cancer, arthritis, Parkinson's disease, diabetes, myocardial infarction and atherosclerosis. The need to understand the role of ROS in these processes is evidenced by the 80,000 publications in this field during the last five years alone. Recently, in a paper James D. Watson called "among my most important work since the double helix,", he posited a theory that links cancer progression in late stages of the disease to the presence of antioxidants and the role of ROS (Watson, J. Open Biol. 2013, 3, 120144). Despite the immense interest and importance of ROS research, there are no probes that combine reliability, sensitivity, and efficiency for detecting ROS in cell culture, ex vivo, and in vivo. No current commercially available probe can image ROS in vivo, which presents a significant impediment in understanding the role of ROS in their native environment (7). Furthermore, there is no probe which can quantitatively image ROS in cell culture or in vivo. A new class of ROS probes, hydrocyanines, has recently been developed and they hold promise of greatly advancing the study of ROS in vitro, ex vivo and in vivo. The principal investigator of this proposal is the original co-inventor of hydrocyanine probes. In orde to enable unprecedented investigations of cellular processes and disease biology, we propose to develop a commercial family of fluorescent hydrocyanine probes, which accurately detects ROS at low nanomolar concentrations in living cells, tissue samples, blood, and for the first time in whole animals. The objective of this project is to develop novel strategies for the hydrocyanines to establish them as highly accurate and robust ROS probes for in vitro and in vivo research applications. For the first time, quantitative imaging of ROS would also be enabled by the development of ratiometric hydrocyanines probes. The specific aims of this project are: Specific Aim I: Develop novel water-soluble hydrocyanines with low background fluorescence Specific Aim II: Validate the novel hydrocyanines in cell-culture Specific Aim III: Develop ratiometric hydrocyanine probes for quantitative ROS imaging Specific Aim IV: Validate ratiometric hydrocyanines in cell-culture The successful completion of this Phase I SBIR project will establish the commercial feasibility of the low background hydrocyanines, and enable LI-COR to provide biomedical researchers with a robust, simple and versatile toolbox to study ROS in any biological sample. In Phase II, hydrocyanine probes will be developed for industrial drug screening and potential clinical diagnostic applications. Ratiometric hydrocyanines for quantitative in vivo imaging of ROS will also be developed in Phase II. We believe that this proposal is ideally suited for the funding opportunity titled "Lab to Marketplace: Tools for Biomedical and Behavioral Research (SBIR [R43/R44])".

描述（由申请人提供）：活性氧（ROS）参与许多细胞信号传导途径。它们与150多种疾病有关，包括癌症、关节炎、帕金森病、糖尿病、心肌梗塞和动脉粥样硬化。仅在过去五年中，这一领域就有80，000篇出版物，这证明需要了解活性氧在这些过程中的作用。最近，在一篇论文中，James D.沃森称之为“自双螺旋以来我最重要的工作之一"，他提出了一种理论，将疾病晚期的癌症进展与抗氧化剂的存在和ROS的作用联系起来（沃森，开放生物学杂志，2013，3，120144）。尽管ROS研究具有巨大的兴趣和重要性，但没有结合联合收割机可靠性、灵敏度和效率的探针用于检测细胞培养物、离体和体内的ROS。目前没有市售的探针可以在体内对ROS成像，这在理解ROS在其天然环境中的作用方面存在重大障碍（7）。此外，没有探针可以定量成像细胞培养物或体内的ROS。最近开发了一类新的ROS探针，氢菁，它们有望大大推进ROS的体外、离体和体内研究。这项提议的主要研究者是氢菁探针的最初共同发明者。为了使前所未有的调查细胞过程和疾病生物学，我们建议开发一个商业家庭的荧光氢菁探针，准确地检测活性氧在低纳摩尔浓度的活细胞，组织样本，血液，并首次在整个动物。本项目的目的是开发新的策略，氢菁，建立他们作为高度准确和强大的活性氧探针在体外和体内的研究应用。对于第一次，定量成像的活性氧也将能够通过开发的比率氢菁探针。本项目的具体目标是：具体目标I：开发具有低背景荧光的新型水溶性氢菁具体目标II：在细胞培养中培养新型氢菁具体目标III：开发用于定量ROS成像的比率氢菁探针具体目标IV：细胞中的三价氢菁-培养该第I阶段SBIR项目的成功完成将确立低背景氢菁的商业可行性，并使LI-COR能够为生物医学研究人员提供一个强大，简单和多功能的工具箱，以研究任何生物样品中的ROS。在第二阶段，氢菁探针将被开发用于工业药物筛选和潜在的临床诊断应用。用于ROS定量体内成像的比率氢菁也将在第二阶段开发。我们认为，该提案非常适合题为“实验室到市场：生物医学和行为研究工具（SBIR [R43/R44]）”的资助机会。