DEVELOPMENT OF RATIOMETRIC IMAGING PROBE SYSTEM FOR MONITORING INFLAMMATION

用于监测炎症的比率成像探头系统的开发

基本信息

批准号：
8312911
负责人：
Wenjing Hu
金额：
$ 21.96万
依托单位：
PROGENITEC, INC.
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-08-15 至 2014-02-14
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8312911
关键词：
Acids Acute Address Adopted Affect Animals Arthritis Asthma Biocompatible Biocompatible Materials Biopsy Blood Burn injury Cells Clinical Dendritic Cells Detection Development Devices Diagnosis Disease Dyes Electron Spin Resonance Spectroscopy Enzyme-Linked Immunosorbent Assay Evaluation Fluorescent Dyes Goals Gunshot wound Hand Human Hyaluronic Acid Hydrogen Peroxide Image Immune In Situ In Vitro Infection Inflammation Inflammatory Inflammatory Response Injury Investigation Link Luminol Lymphocyte Malignant Neoplasms Measurement Mediating Methods Modeling Monitor Myocardial Infarction Optics Pathogenesis Patient Care Patients Procedures Process Production Reaction Reactive Oxygen Species Recruitment Activity Respiratory Burst Role Series Signal Transduction Site Source Stimulus Superoxides Syndrome System Techniques Testing Time Tissues Trauma Variant White Blood Cell Count procedure Work Wound Healing base cytokine design imaging probe improved in vitro activity in vivo injured killings macrophage mast cell microorganism monocyte nanoparticle neutrophil non-invasive monitor novel oxidative damage particle ratiometric sensor subcutaneous tool wound

项目摘要

DESCRIPTION (provided by applicant): Inflammation is a major unifying syndrome associated with a variety of injury and diseases. When severe, inflammatory diseases can endanger and even kill patients. Direct diagnosis of the extent of inflammatory responses is often made histological with an invasive biopsy. Furthermore, multiple biopsies are often required to assess the extent of inflammatory reactions in a large wound. The proposed work is aimed at developing a new non-invasive method to assess the extent of inflammatory responses in real-time in vivo. Reactive oxygen species (ROS) released by polymorphonuclear neutrophils have been shown to be a good indicator of the degree of inflammatory reactions. Several ROS-reactive bioluminescent probes have been investigated in recent years to detect ROS activities in vivo. Unfortunately, these probes alone cannot be used to quantify the degree of inflammatory responses due to the fact that the extent of the bioluminescent signals is also probe-concentration dependent. To address this challenge, we adopt ratiometric probe technique in which both ROS-sensitive agents and ROS-insensitive reference dye are conjugated to biocompatible particle carriers. The bioluminescent/reference fluorescent intensity ratios can be calculated to reflect the extent of localized ROS activities while circumventing the variations of bioluminescent intensities associated with the ROS probe concentrations. Our preliminary studies have led to the development of ROS ratiometric probes which can reliably detect localized ROS activities in vivo and inflamed tissue in the wound site. Based on these exciting observations, the proposed work will create a series of ROS ratiometric probes to detect ROS activities in vitro (Aim 1) and to assess the extent of inflammatory responses mediated by different injuries or inflammatory stimuli in vivo (Aim 2). Finally, since all commercial imagers are designed with an enclosed chamber only suitable for cell and small animal imaging, a handheld imager for ROS sensing in large animals and human will be developed as part of this investigation. The successful completion of this proposed work will help the development of a new diagnosis tool which can be applied to non-invasively monitor the inflammatory processes in real-time and assist the development of new treatments to effectively reduce inflammation and improve wound healing reactions. PUBLIC HEALTH RELEVANCE: A series of novel reactive oxygen species (ROS) ratiometric imaging probes and a hand-held optical device will be fabricated to monitor and quantify in situ ROS activities and associated inflammatory responses in vivo. The successful completion of the proposed work will help the development of a new diagnosis tool which can be effectively used to non-invasively assess the extent of inflammatory processes in real-time and substantially improve the quality of patient care.

描述（由申请人提供）：炎症是与多种损伤和疾病相关的主要统一综合征。严重时，炎症性疾病会危及甚至杀死患者。炎症反应程度的直接诊断通常通过侵入性活检进行组织学诊断。此外，通常需要进行多次活检来评估大伤口的炎症反应程度。拟议的工作旨在开发一种新的非侵入性方法来实时评估体内炎症反应的程度。多形核中性粒细胞释放的活性氧（ROS）已被证明是炎症反应程度的良好指标。近年来，人们研究了几种 ROS 反应性生物发光探针来检测体内 ROS 活性。不幸的是，由于生物发光信号的程度也依赖于探针浓度，因此这些探针不能单独用于量化炎症反应的程度。为了应对这一挑战，我们采用比例探针技术，其中 ROS 敏感剂和 ROS 不敏感参考染料均与生物相容性颗粒载体缀合。可以计算生物发光/参考荧光强度比，以反映局部 ROS 活性的程度，同时避免与 ROS 探针浓度相关的生物发光强度的变化。我们的初步研究导致了 ROS 比例探针的开发，它可以可靠地检测体内局部 ROS 活性和伤口部位的发炎组织。基于这些令人兴奋的观察结果，拟议的工作将创建一系列ROS比率探针来检测体外ROS活性（目标1）并评估体内不同损伤或炎症刺激介导的炎症反应程度（目标2）。最后，由于所有商业成像仪均设计有仅适用于细胞和小动物成像的封闭室，因此作为本研究的一部分，将开发用于大型动物和人类 ROS 传感的手持式成像仪。这项工作的成功完成将有助于开发一种新的诊断工具，该工具可用于非侵入性地实时监测炎症过程，并协助开发新的治疗方法，以有效减少炎症并改善伤口愈合反应。公共健康相关性：将制造一系列新型活性氧 (ROS) 比率成像探针和手持式光学设备，以监测和量化原位 ROS 活性和体内相关炎症反应。拟议工作的成功完成将有助于开发一种新的诊断工具，该工具可有效地用于非侵入性地实时评估炎症过程的程度，并大幅提高患者护理的质量。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Canny edge-based deformable image registration.

DOI：
10.1088/1361-6560/aa5342
发表时间：
2017-02-07
期刊：
Physics in medicine and biology
影响因子：
3.5
作者：
Kearney V;Huang Y;Mao W;Yuan B;Tang L
通讯作者：
Tang L

Ratiometric Reactive Oxygen Species Nanoprobe for Noninvasive In Vivo Imaging of Subcutaneous Inflammation/Infection.

DOI：
10.1166/jbn.2016.2268
发表时间：
2016-08
期刊：
Journal of biomedical nanotechnology
影响因子：
2.9
作者：
Zhou J;Weng H;Huang Y;Gu Y;Tang L;Hu W
通讯作者：
Hu W

Optical imaging of fibrin deposition to elucidate participation of mast cells in foreign body responses.

DOI：
10.1016/j.biomaterials.2013.11.040
发表时间：
2014-02
期刊：
BIOMATERIALS
影响因子：
14
作者：
Tsai, Yi-Ting;Zhou, Jun;Weng, Hong;Tang, Ewin N.;Baker, David W.;Tang, Liping
通讯作者：
Tang, Liping

Design of a portable imager for near-infrared visualization of cutaneous wounds.

设计用于皮肤伤口近红外可视化的便携式成像仪。

DOI：
10.1117/1.jbo.22.1.016010
发表时间：
2017
期刊：
Journal of biomedical optics
影响因子：
3.5
作者：
Peng,Zhaoqiang;Zhou,Jun;Dacy,Ashley;Zhao,Deyin;Kearney,Vasant;Zhou,Weidong;Tang,Liping;Hu,Wenjing
通讯作者：
Hu,Wenjing

Development of a dual-wavelength fluorescent nanoprobe for in vivo and in vitro cell tracking consecutively.