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、经济、快速的成像方式，可以多路复用或工程化