Selenium-based electrocatalytic sensors for sensitive peroxynitrite detection in biological media: a bottom-up approach for functional interface design

用于生物介质中敏感过氧亚硝酸盐检测的硒基电催化传感器：功能界面设计的自下而上方法

• 批准号: 10799038
• 负责人: MEKKI BAYACHOU
• 金额: $ 10万
• 依托单位: CLEVELAND STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10799038
• 关键词: Administrative Supplement; Adult; Affect; Biochemical; Biocompatible Materials; Biological; Cardiovascular Diseases; Cell membrane; Cell physiology; Cells; Cessation of life; Chemicals; Chronic; Clinical; Collection; Coupled; DNA; Detection; Development; Devices; Disease; Electrodes; Electronics; Equipment; Film; Funding; Goals; Grant; Hot Spot; Image; Immune response; In Situ; Inflammation; Libraries; Link; Lipids; Liposomes; Maps; Measurement; Measures; Membrane Lipids; Methods; Microscope; Miniaturization; Modeling; Molecular; Monitor; Morbidity - disease rate; National Institute of General Medical Sciences; Natural graphite; Nitric Oxide; Oxidative Stress; Parents; Pathologic; Pathology; Performance; Peroxonitrite; Physiological; Physiological Processes; Process; Property; Proteins; Reaction; Reporting; Reproducibility; Research; Resolution; Role; Scanning; Scanning Probe Microscopes; Selenium; Sepsis; Signal Transduction; Source; Superoxides; Surface; System; Techniques; Testing; Thinness; Time; United States; United States National Institutes of Health; Vasodilation; Work; assault; biological systems; carbon fiber; cytotoxic; design; in vivo; instrument; interest; microsensor; miniaturize; miniaturized sensor; mortality; mortality statistics; oxidation; parent grant; sensor; stress reactivity; tool

Project Summary: Biological Background and the Challenge: Peroxynitrite (OONO-) is a potent cytotoxic compound that has been implicated in a host of pathophysiological conditions. Peroxynitrite is the primary product of the in vivo reaction of nitric oxide and superoxide anion-radical. The multifaceted physiologic reactions of this compound are directly implicated in a number of pathologies including, immune response, chronic inflammation, sepsis, and cardiovascular disease, to cite a few. just cardiovascular disease alone claims about 7 deaths every 4 minutes and sepsis affects 1.7 million adults in the United States each year and contributes to more than 250,000 deaths. The common thread that links peroxynitrite to all cited pathologies is its potent reactivity toward most cellular components including DNA, proteins, and lipids in cell membranes. Substantial oxidations and other transformations of proteins, DNA, and lipids contribute to the disruption of key cellular functions. The task of assessing peroxynitrite’s deleterious effects and examining hypotheses of its potential signaling roles is very difficult. The primary reason is that methods for measuring and monitoring accurately its concentration are inherently difficult due to low submicromolar concentrations under physiologic conditions coupled with its high reactivity. The electrochemical detection of peroxynitrite is a simpler and more convenient technique for application in biological settings. However, a systematic development of the right electrode interface that enhances the sensitivity and selectivity for this molecule is lacking. In the ongoing work of the parent grant we develop electrode interfaces decorated with organoselenides attached to the surface that serve as catalytic entities for sensitive and selective PON electrocatalytic determination. The request of this Administrative Supplement: Funds are requested to purchase an Electrochemical Scanning Probe Microscope (SECM) Equipment that is critical for the completion of aspects of specific Aims 2 and Specific Aim3 of the current NIH project. The equipment model is the ElProScan ELP electrochemical scanning microscope and related accessories. The SECM equipment is a unique scanning probe microscope system that uses micro- and ultramicrolectrodes as scanning probes in order to measure with high spatial resolution and accuracy local current measurement (activity/election exchange) over substrates of interest (in this case substrates in the form of liposomes of live single cells that generate peroxynitrite upon stimulation). The Request is to Support Work Well Within the Scope of the Current NIGMS-funded Grant: The requested equipment will be used in a manner to generate high-resolution topographic imaging in the form of electrochemical activity as a result of peroxynitrite release (see the accompanying 2-page Research Strategy). The instrument will be used in a variety of ways: 1) it will be used to test miniaturized sensors based on the most active selenides as developed in this work. 2) The equipment will also be used to test the most optimal sensors for PON measurement over live single cells. 3) We will also use the instrument over collections of cells. All of these ways will support aspects of Specific Aim2 and particularly Specific Aim3 as explained in Research Strategy section. The electrochemical scanning probe microscope that we request is compatible and will be mounted on our existing Olympus inverted microscope. This will allow us to easily and reproducibly validate the performance of our miniaturized selenide-based peroxynitrite sensors on biological sources of peroxynitrite. The setup will allow us to carry out scanning and current measurement at the same time and with high temporal and spatial resolution on biological materials such as live single cells and collections of cells as well lipid membranes of cell-like (NOS-Loaded Liposomes) as we described in our parent NIH project that is underway.

项目摘要： 生物背景与挑战：过氧亚硝酸盐（OONO-）是潜在的细胞毒性化合物 在许多病理生理状况中暗示了这一点。过氧亚硝酸盐是 一氧化氮和超氧化阴离子 - 激进的体内反应。多方面的生理反应 该化合物直接与许多病理有关，包括免疫响应，慢性 炎症，败血症和心血管疾病，引用一些。仅凭心血管疾病就声称 每4分钟约7人死亡，败血症每年影响170万成年人， 导致25万多人死亡。将过氧亚硝酸盐连接到所有引用的共同线程 病理是其对大多数细胞成分的潜在反应性，包括DNA，蛋白质和脂质 细胞膜。蛋白质，DNA和脂质的大量氧化和其他转化有助于 关键细胞函数的破坏。 评估过氧亚硝酸盐的有害效果并研究其潜力的假设的任务 信号角色非常困难。主要原因是准确测量和监视的方法 由于生理学下的亚微摩尔浓度较低，其浓度本质上很难 条件与其高反应性相结合。过氧亚硝酸盐的电化学检测更简单，并且 在生物环境中应用的更便捷的技术。但是，一个系统的发展 缺乏提高对该分子的灵敏度和选择性的右电极界面。在 父母赠款正在进行的工作，我们开发了带有有机素的电极界面 作为敏感和选择性PON电催化测定的催化实体的表面。 此行政补充的要求： 要求资金购买电化学扫描探针显微镜（SECM）设备 对于完成当前NIH项目的特定目标2和特定AIM3的各个方面至关重要。这 设备模型是Elproscan ELP电化学扫描显微镜和相关配件。 SECM设备是一种独特的扫描探针显微镜系统，使用微型和微观 超细菌作为扫描问题，以便以高空间分辨率和准确性局部测量 当前的测量（活动/选举交换）对利益的基板（在这种情况下，在这种情况下 活的单细胞的脂质体形式在刺激时会产生过氧亚硝酸盐）。 该请求是在当前的NIGMS资助赠款的范围内提供良好的工作： 请求的设备将以某种方式用于生成高分辨率地形图像 过氧亚硝酸盐释放后的电化学活性形式（请参阅参与的2页 研究策略）。该仪器将以多种方式使用：1）将用于测试小型化 基于这项工作中开发的最活跃的硒化的传感器。 2）设备也将被使用 测试对活单元的最佳传感器进行PON测量。 3）我们还将使用 仪器遍布细胞的集合。所有这些方式都将支持特定AIM2的各个方面，特别是 特定的AIM3如研究策略部分所述。 我们要求兼容的电化学扫描探针显微镜，将安装在我们的 现有的奥林巴斯倒立显微镜。这将使我们能够轻松且可重复地验证 在生物学来源上的微型硒化过氧量传感器的性能 过氧亚硝酸盐。该设置将使我们能够同时进行扫描和当前测量 在生物材料（例如活细胞）上具有高临时和空间分辨率 细胞以及细胞状的脂质膜（NOS载的脂质体），如我们在父级NIH中所述 正在进行的项目。

项目成果

Inducible Nitric Oxide Synthase Embedded in Alginate/Polyethyleneimine Hydrogel as a New Platform to Explore NO-Driven Modulation of Biological Function.

• DOI: 10.3390/molecules28041612
• 发表时间: 2023-02-07
• 期刊: MOLECULES
• 影响因子: 4.6
• 作者: Maher, Shaimaa;Smith, Lauren A.;El-Khoury, Celine A.;Kalil, Haitham;Sossey-Alaoui, Khalid;Bayachou, Mekki
• 通讯作者: Bayachou, Mekki

Microspheres with 2D rGO/Alginate Matrix for Unusual Prolonged Release of Cefotaxime.

• DOI: 10.3390/nano13091527
• 发表时间: 2023-05-01
• 期刊: Nanomaterials (Basel, Switzerland)
• 作者: Gomaa I;Emam MH;Wassel AR;Ashraf K;Hussan S;Kalil H;Bayachou M;Ibrahim MA
• 通讯作者: Ibrahim MA