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Circulating Red Blood Cell Based Nanosensors for Continuous, Real-Time Drug Monitoring

基于循环红细胞的纳米传感器，用于连续、实时药物监测

基本信息

批准号：
10174441
负责人：
Heather A Clark
金额：
$ 21.11万
依托单位：
NORTHEASTERN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-02-01 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10174441
关键词：
Adopted Animal Experimentation Animals Articular Range of Motion Base Pairing Biochemical Biological Biological Markers Blood Tests C-reactive protein COVID-19 Chemicals Coronavirus Infections DNA DNA Modification Process DNA Structure Detection Development Diagnostic Digestion Disease Drug Monitoring Early Diagnosis Environment Erythrocytes Event Ferritin Goals Immune system Immunologics Interferon Type II Interleukin-10 Interleukin-6 Laboratories Measurement Mechanics Methods Modification Monitor Morbidity - disease rate Nanostructures Nanotechnology Optics Organ Outcome Pathogenesis Pathogenicity Patients Performance Proteins Publishing Research Research Personnel Resistance Serum Severe Acute Respiratory Syndrome Signal Transduction Site Surface Symptoms T cell therapy Technology Testing Therapeutic Intervention Time Treatment Efficacy Viral Pathogenesis Work arm base chemical stability clinical diagnostics cytokine cytokine release syndrome design diagnosis standard diagnostic assay flexibility fluorescence imaging imaging modality imaging platform improved in vivo in vivo monitoring mechanical properties minimally invasive nanosensors novel nuclease optical imaging photoacoustic imaging predictive marker prevent receptor response scaffold sensor spatiotemporal systemic inflammatory response systems research tool

项目摘要

ABSTRACT Nanosensor technology for continuous monitoring of proteins in vivo would enable researchers to track the dynamics of biomolecule expression as it pertains to disease pathogenesis or predicting therapeutic efficacy, with results available in real-time. An example where this diagnostic ability would be groundbreaking is in the context of understanding cytokine release syndrome (CRS). CRS is a systemic inflammatory response that arises when the immune system is overstimulated, leading to extreme toxic events such as multiple organ dysfunction1. There is now increasing evidence to suggest that the development of severe cases of COVID-19 can be attributed to onset of CRS. It has been revealed that serum levels of cytokines like IFNγ, IL-6, sIL-2Rα, and IL-10 can be significantly elevated in patients with severe CRS, before the apparent onset of severe symptoms. However, the use of cytokines as biomarkers of CRS would require a rapid, minimally invasive diagnostic assay, which is currently unavailable, slowing animal studies of COVID-19/CRS. Recently published research from the Clark laboratory has demonstrated a proof-of-concept DNA-based sensor for minimally invasive detection of IFNγ, one of the cytokines that has been proposed as a biomarker for predicting the potential for onset of severe CRS. This design was inspired by advances in DNA nanotechnology, which enable researchers to create functional nanostructures with site-specific modifications based on the complementary base-pairing rules of DNA. The open or closed state of the sensor could be determined through differential signals as detected with optical imaging. Drawing from recent advances in DNA origami design and stabilization technology, we hypothesize that we can improve on this work and produce a robust platform for optical monitoring of IFNγ in real-time by (1) enhancing the rigidity of our DNA platform and (2) deploying protection strategies to ionically stabilize the construct in biological solutions. This project aims to advance current analytical strategies for immunological diagnostics by providing researchers with a powerful tool to probe biomolecule dynamics toward in vivo use with existing optical imaging platforms. The one-year project will result in a robust tool developed for animal research. The goal will be to commercialize and distribute the sensor for COVID-19 studies, as well as other immune system research.

抽象的用于连续监测体内蛋白质的纳米传感器技术将使研究人员能够跟踪与疾病发病机制或预测治疗效果有关的生物分子表达动态，并实时提供结果。这种诊断能力具有开创性的一个例子是了解细胞因子释放综合征（CRS）的背景。 CRS 是一种全身性炎症反应，当免疫系统受到过度刺激时就会出现，导致极端毒性事件，例如多器官功能障碍1.现在有越来越多的证据表明，COVID-19 重症病例的发展可以归因于 CRS 的发生。研究表明，血清中 IFNγ、IL-6、sIL-2Rα 等细胞因子的水平在严重 CRS 患者明显出现严重症状之前，IL-10 和 IL-10 会显着升高。症状。然而，使用细胞因子作为 CRS 的生物标志物需要一种快速、微创的方法。目前尚不可用的诊断测定，减缓了 COVID-19/CRS 的动物研究。最近发表克拉克实验室的研究证明了一种基于 DNA 的概念验证传感器 IFNγ 的侵入性检测，IFNγ 是一种细胞因子，已被提议作为预测疾病的生物标志物发生严重 CRS 的可能性。该设计的灵感来自 DNA 纳米技术的进步，该技术使研究人员基于互补性创建具有位点特异性修饰的功能纳米结构 DNA 的碱基配对规则。传感器的打开或关闭状态可以通过微分来确定通过光学成像检测到的信号。借鉴 DNA 折纸设计和稳定性的最新进展技术，我们假设我们可以改进这项工作并为光学提供一个强大的平台通过 (1) 增强 DNA 平台的刚性和 (2) 部署保护来实时监测 IFNγ 在生物溶液中离子稳定构建体的策略。该项目旨在推进当前的分析通过为研究人员提供探测生物分子的强大工具来制定免疫诊断策略现有光学成像平台的体内使用动态。这个为期一年的项目将带来强劲的成果为动物研究开发的工具。目标是将用于 COVID-19 的传感器商业化和分销研究以及其他免疫系统研究。