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.

项目总结:

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