Biocompatible fluorophores for shortwave infrared imaging

用于短波红外成像的生物相容性荧光团

• 批准号: 10321256
• 负责人: Ellen May Sletten
• 金额: $ 34.27万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-01 至 2023-09-12
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10321256
• 关键词: Animal Model; Behavior; Benchmarking; Carbon Nanotubes; Clinic; Clinical; Clinical Trials; Contrast Media; Development; Diagnostic; Diagnostic Procedure; Disease; Dyes; Early Diagnosis; Electromagnetics; Electronics; Emulsions; Endoscopes; Engineering; FDA approved; Fluorescence Resonance Energy Transfer; Fluorocarbons; Formulation; Foundations; Generations; Image Enhancement Agent; Image-Guided Surgery; In Vitro; Indocyanine Green; Lead; Libraries; Light; Link; Mammals; Mammography; Methods; Modification; Noise; Optics; Organism; Outcome; Patients; Penetration; Peptide Hydrolases; Performance; Property; Quantum Dots; Rapid diagnostics; Reporting; Resolution; Shortwave Infrared Imaging; Signal Transduction; Silicon; Stimulus; Structure; Survival Rate; Tissues; Toxic effect; Variant; Water; Work; absorption; base; biomaterial compatibility; chromophore; clinical application; clinical implementation; clinical optical imaging; clinical translation; cost; cost effective; disease diagnosis; experimental study; fluorophore; imaging agent; imaging modality; improved; in vivo; interest; light scattering; multiplexed imaging; nanomaterials; novel; optical imaging; preclinical study; prevent; protein aminoacid sequence; quantum; redshift; response; scaffold; spatiotemporal; success; targeted agent; targeted imaging

Optical imaging is a safe, cost-effective, rapid imaging modality, which can be multiplexed or engineered to have a turn-on response. Despite these advantages, optical imaging is not widely employed in the clinic due to the poor penetration of light through tissue and high background signal from endogenous chromophores. The shortwave infrared (SWIR) region of the electromagnetic spectrum has emerged as an optimal region for optical imaging due to the decreased scattering of light by tissue and minimal autofluorescence of endogenous biomolecules in this region. The potential of the SWIR has been showcased using carbon nanotubes and quantum dots as contrast agents; however, toxicity concerns regarding these materials prevent their clinical translation. What is necessary are bright, non-toxic shortwave infrared fluorophores. Recently, we have reported a bright polymethine fluorophore, deemed Flav7, which absorbs and emits shortwave infrared light. We will take this exciting first generation compound and transform Flav7 into a water- soluble contrast agent that can be appended to targeting agents and biomolecules of interest. We will improve nanomaterial formulations of Flav7 by synthesizing fluorous-soluble variants. Simultaneously, we will modify the chromophore structure to enhance the photophysical properties and access fluorophores that can be employed simultaneously for multiplexed SWIR imaging. Lastly, we will develop SWIR quenchers, which will be linked to the fluorophores using protease-cleavable peptide sequences to access SWIR responsive probes. Responsive probes offer enhanced signal-to-noise ratios and eliminate the need to wait for fluorophores to clear. Visible and near-infrared versions of similar responsive probes are currently in clinical trials for image- guided surgery. Collectively, our fluorophore development work will provide the foundation for intraoperative imaging, fluorescent endoscope-based diagnostics, and optical mammography.

光学成像是一种安全，成本效益的快速成像方式，可以多路复用或设计为 有一个转响应。尽管有这些优势，但由于 通过组织中的光穿透不良和内源性发色团的高背景信号。这 电磁光谱的短波红外（SWIR）区域已成为最佳区域 由于通过组织减少光的光散射和内源性的最小自动荧光而导致光学成像 该地区的生物分子。使用碳纳米管和 量子点作为对比剂；但是，关于这些材料的毒性问题阻止了其临床 翻译。必要的是明亮的，无毒的短波红外荧光团。 最近，我们报道了一种明亮的多胸荧光团，被认为是Flav7，可吸收和发射 短波红外光。我们将将这种令人兴奋的第一代化合物和转化为水 - 可溶性对比剂可以附加到目标剂和生物分子的目标。我们将有所改善 Flav7的纳米材料制剂通过合成荧光溶质变体。同时，我们将修改 发色团结构，以增强可以是的光物理特性和访问荧光团 同时用于多路复用SWIR成像。最后，我们将开发Swir Quenchers，这将 使用蛋白酶可裂化的肽序列与荧光团链接，以访问SWIR响应探针。 响应式探针提供了提高的信号噪声比率，并消除了等待荧光团的需求 清除。当前，类似反应探针的可见和近红外版本正在用于图像的临床试验中 指导手术。总的来说，我们的荧光团发展工作将为术中奠定基础 成像，基于荧光内窥镜的诊断和光乳房X线摄影。