Development of Nanosensors to Image Macrophage Polarization

开发巨噬细胞偏振成像纳米传感器

• 批准号: 10460691
• 负责人: Laura J Suggs
• 金额: $ 49.73万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-03 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10460691
• 关键词: Amputation; Anti-Inflammatory Agents; Antibody Therapy; Antioxidants; Arterial Fatty Streak; Arteries; Biocompatible Materials; Biological; Blood flow; Cardiovascular Diseases; Cells; Cleaved cell; Development; Diagnosis; Diagnostic; Disease; Disease Progression; Dyes; Energy Transfer; Enzymes; Event; Exhibits; Fluorescence; Generations; Goals; Gold; Image; In Situ; In Vitro; Inflammation; Inflammatory; Inflammatory Response; Injury; Length; Limb structure; Magnetic Resonance Imaging; Measures; Modeling; Molecular; Monitor; Multimodal Imaging; Mus; Optics; Outcome; Patients; Penetration; Peripheral arterial disease; Pharmacotherapy; Phenotype; Photons; Positron-Emission Tomography; Predisposition; Procedures; Process; Radioactive; Reactive Oxygen Species; Reperfusion Injury; Reperfusion Therapy; Resolution; Role; Sensitivity and Specificity; Signal Transduction; Structure; Surface; Testing; Time; Tissue imaging; Tissues; Tracer; Treatment Efficacy; Ultrasonography; base; bioluminescence imaging; biomaterial compatibility; critical limb Ischemia; experience; fluorescence imaging; fluorophore; healing; high resolution imaging; imaging approach; imaging modality; immunomodulatory therapies; in vivo; in vivo imaging; interest; limb loss; macrophage; migration; millisecond; mortality; multiplexed imaging; nanoGold; nanoparticle; nanoprobe; nanorod; nanosensors; non-invasive imaging; novel; oxidative damage; photoacoustic imaging; preclinical study; real-time images; single photon emission computed tomography; success; three-dimensional visualization; tool

Project Summary Peripheral artery disease (PAD) is a form of cardiovascular disease in which atherosclerotic plaque builds up within the arteries of the body. PAD reduces blood flow to the extremities and can progress to critical limb ischemia (CLI) and, ultimately, loss of limb. Revascularization procedures are commonly used to salvage the ischemic tissue, and while they restore blood flow, the reperfusion of tissues induces additional injury, resulting in severe inflammation and oxidative damage that can contribute to a cycle of further damage and disease. Recent preclinical studies have therefore evaluated drug therapies in combination with revascularization in order to control the inflammatory cascade. In order to understand disease progression and subsequent healing, it is critically important to be able to visualize inflammatory processes in situ. In particular, inflammatory cells such as macrophages exhibit multiple, competing phenotypic states depending on their local, transient microenvironment. It would therefore be ideal to non-invasively image macrophage phenotypic changes over time as a result of disease or healing progression. Current imaging approaches have either low sensitivity or spatial resolution, or both. Therefore, there is a need for non-invasive real-time imaging of macrophages in vivo with high sensitivity, specificity, depth penetration and resolution. Our group has developed nanoparticle-augmented combined ultrasound and photoacoustic (US/PA) imaging which has advantages over current imaging approaches. In particular, US/PA imaging can help to visualize and monitor a highly orchestrated set of events in inflammation ranging from milliseconds to days. High-resolution imaging of tissue is possible, and signals can be acquired over a reasonably large volumetric region of interest, permitting 3D visualization of tissue structures. Finally, using non-toxic, biocompatible nanoconstructs consisting of optical dyes, gold nanoparticles, and other biocompatible materials, cellular and molecular US-guided PA imaging is possible. Therefore, US/PA imaging with the appropriate nanosensors has the potential to become an important tool of sufficient sensitivity and specificity for studying inflammation in general and macrophage polarization in particular. The overall goal of this proposal is to develop and test a unique suite of nanoparticle-based probes that are sensitive to macrophage polarization state and can be visualized in vivo using high-resolution, multiplex US/PA imaging.

项目摘要 外周动脉疾病（PAD）是一种心血管疾病，其中动脉粥样硬化性心脏病是一种常见的心血管疾病。 斑块在身体的动脉内积聚。PAD减少了流向四肢的血液， 发展为严重肢体缺血（CLI），并最终丧失肢体。血运重建手术是 通常用于挽救缺血组织，当它们恢复血流时， 组织诱导额外的损伤，导致严重的炎症和氧化损伤， 导致进一步的损害和疾病循环。因此，最近的临床前研究评估了 药物治疗与血管重建相结合，以控制炎症级联反应。在 为了了解疾病进展和随后的愈合，能够 可视化原位炎症过程。特别地，炎性细胞如巨噬细胞表现出 多个竞争性的表型状态取决于它们局部的短暂微环境。它将 因此，理想的是非侵入性成像巨噬细胞表型随时间的变化， 疾病或愈合进展。当前的成像方法具有低灵敏度或空间分辨率。 决议，或两者。因此，需要对体内巨噬细胞进行无创实时成像 具有高灵敏度、特异性、穿透深度和分辨率。 我们的小组已经开发出纳米颗粒增强的组合超声和光声 (US/PA）成像，其具有优于当前成像方法的优点。特别是，US/PA成像 可以帮助可视化和监测炎症中一系列高度协调的事件， 毫秒到几天组织的高分辨率成像是可能的，并且信号可以在一个或多个时间段上被采集。 合理大的感兴趣体积区域，允许组织结构的3D可视化。最后， 使用由光学染料、金纳米颗粒和其他材料组成的无毒、生物相容的纳米结构， 生物相容性材料、细胞和分子超声引导PA成像是可能的。美国/PA 用适当的纳米传感器成像有可能成为一种重要的工具， 用于研究一般炎症和特别是巨噬细胞极化的灵敏度和特异性。 该提案的总体目标是开发和测试一套独特的基于纳米颗粒的探针， 对巨噬细胞极化状态敏感，并且可以使用高分辨率在体内可视化， 多路超声/PA成像。