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

• 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
• 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

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，炎症性疾病可能危及甚至杀死患者。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检查。此外，通常需要多次活检来评估大伤口中炎症反应的程度。拟议的工作旨在开发一种新的非侵入性方法来评估体内实时炎症反应的程度。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是探针浓度依赖性的事实，这些探针不能单独用于量化炎症反应的程度。为了解决这一挑战，我们采用比率探针技术，其中ROS敏感剂和ROS不敏感的参比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。我们的初步研究已经导致ROS比率探针的发展，它可以可靠地检测局部活性氧在体内和伤口部位的发炎组织的活动。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的程度（目标2）。最后，由于所有商业成像仪都设计有一个封闭的腔室，仅适用于细胞和小动物成像，在大型动物和人类的ROS传感手持成像仪将开发作为本调查的一部分。这项工作的成功完成将有助于开发一种新的诊断工具，该工具可用于实时无创监测炎症过程，并有助于开发新的治疗方法，以有效减少炎症并改善伤口愈合反应。 公共卫生关系：一系列新的活性氧（ROS）比率成像探针和手持光学装置将被制造来监测和定量原位ROS活性和相关的体内炎症反应。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实时非侵入性评估炎症过程的程度，并大大提高患者护理质量。

项目成果

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

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

• DOI: 10.1016/j.bmc.2019.03.036
• 发表时间: 2019-05
• 期刊: Bioorganic & medicinal chemistry
• 影响因子: 3.5
• 作者: Hong Vu;Jun Zhou;YiHui Huang;Amirhossein Hakamivala;M. Khang;Liping Tang

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

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