High-throughput Integrated Magneto-electrochemical Exosome (HiMEX) platform to identify neurodevelopmental markers associated with pre and postnatal oxycodone exposure

高通量集成磁电化学外泌体 (HiMEX) 平台，用于识别与产前和产后羟考酮暴露相关的神经发育标志物

• 批准号: 10017043
• 负责人: Hakho Lee
• 金额: $ 21.07万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-30 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10017043
• 关键词: Address; Affect; Animals; Berry; Biological Assay; Biological Markers; Biology; Blood Tests; Brain; Cell Line; Cells; Child; Clinical; Cognition Disorders; Complement; Core Facility; Coupled; Data; Detection; Development; Diagnostic; Drug Exposure; Drug abuse; Elements; Enzyme-Linked Immunosorbent Assay; Etiology; Exposure to; Fostering; Functional disorder; Generations; Goals; Growth; Health; Impairment; In Vitro; Infant Care; Institution; Intervention; Knowledge; Lactation; Lipids; Measurement; Membrane; Molecular Profiling; Monitor; Mothers; Neonatal; Newborn Infant; Nucleic Acids; Opioid; Outcomes Research; Oxycodone; Pain; Pathway interactions; Plasma; Pregnancy; Prevention; Principal Investigator; Proteins; Proteome; Proteomics; Rattus; Research; Risk; Risk Assessment; Rodent Model; Saline; Sampling; Signal Transduction; Solid; Substance Use Disorder; Substance Withdrawal Syndrome; System; Technology; Testing; Time; Translating; United States; Validation; Vesicle; base; bioinformatics tool; biomarker discovery; blood-based biomarker; brain cell; brain dysfunction; brain research; candidate marker; clinical care; cost; detector; differential expression; drug withdrawal; exosome; experience; extracellular vesicles; high risk; improved; in utero; innovation; insight; instrument; maternal opioid use; minimally invasive; molecular marker; nanoplasmonic; neonatal care; neonate; neurodevelopment; neuroimaging; next generation; novel diagnostics; novel marker; offspring; opioid use; particle; postnatal; pre-clinical; prenatal; prescription opioid; prescription opioid abuse; prescription opioid addiction; prescription opioid misuse; screening; sensor; success; synaptogenesis; technology development

Dependency on prescription opioids during and after pregnancy poses a significant health risk, both to mother and child. Newborns exposed to opioids would experience a drug withdrawal syndrome and have elevated risk of cognitive disorders. Clinical care for these exposed neonates, however, is challenged by a current fundamental gap in knowledge: lack of reliable biomarkers available to objectively assess newborn's risk from drug-exposure: it is poorly understood how pre- and postnatal opioid use affects offsprings, particularly with neurodevelopment, and no reliable biomarkers are available to objectively assess a newborn's risk from drug- exposure. We seek to advance a new assay platform to effectively monitor newborns' exposure to oxycodone (oxy). Our approach will be based on two innovative approaches: extracellular vesicles (EVs) as a biomarker and iMEX (integrated magneto-electrochemical exosome) as a sensor platform. Aim 1. We will identify EV protein signatures of high-risk oxy-exposure. We will use our rodent models to emulate in-utero and postnatal oxy-exposures. EVs from brains of oxy-exposed offspring will be collected and analyzed via quantitative proteomics to identify differentially-expressed proteins. Aim 2. We will implement the second generation iMEX with significantly expand analytical capacities. We will enhance iMEX detection sensitivity by exploring a new signal amplification (nanoplasmonics); establish a unified assay to detect both transmembrane and intravesicular markers; and construct a high-throughput detector (a 96 well-plate format). This new system will be used to screen plasma EVs from oxy-exposed animals. The success of this project will generate comprehensive protein data on brain-derived EVs under oxy-exposure and critically EVs' potential as a biomarker. Furthermore, the insights gained will set the stage to further extend HiMEX technology for clinical validation. Our long-term goal is to deliver a minimally-invasive blood test for risk assessment and timely intervention for oxy-exposure.

怀孕期间和之后对处方阿片类药物的依赖对母亲构成重大健康风险 和孩子。接触阿片类药物的新生儿会患有药物戒断综合症，风险升高 认知障碍。但是，这些暴露的新生儿的临床护理受到当前的挑战 知识的根本差距：缺乏可靠的生物标志物来客观地评估新生儿的风险 药物暴露：鲜为人知的是前后阿片类药物的使用如何影响后代，尤其是在 神经发育，没有可靠的生物标志物可以客观地评估新生儿的药物风险 接触。我们试图推进一个新的测定平台，以有效监测新生儿接触羟考酮 （氧）。我们的方法将基于两种创新的方法：细胞外囊泡（EV）作为生物标志物 和IMEX（集成的磁性电化学外显体）作为传感器平台。目标1。我们将确定EV 高危氧气暴露的蛋白质特征。我们将使用我们的啮齿动物模型模仿Utero和产后 氧气曝光。将通过定量收集和分析来自氧气暴露后代的大脑的电动汽车 蛋白质组学鉴定差异表达的蛋白质。目标2。我们将实施第二代IMEX 具有显着扩大分析能力。我们将通过探索新的 信号扩增（纳米浮雕）；建立一个统一的测定法以检测跨膜和 插入式标记；并构建高通量检测器（96个固定板格式）。这个新系统将 用于从暴露于氧气的动物中筛选等离子体电动汽车。该项目的成功将产生 有关氧气暴露和关键EV的潜力作为脑源性电动汽车的综合蛋白质数据 生物标志物。此外，获得的见解将为进一步扩展HIMEX技术的舞台奠定基础 验证。我们的长期目标是为风险评估和及时提供最低侵入性的血液测试 干预氧气暴露。