Biocompatible fluorophores for shortwave infrared imaging

光学成像是一种安全、经济、快速的成像方式，它可以被多路传输或设计成 有一个兴奋的反应。尽管有这些优点，光学成像在临床上并没有得到广泛的应用，因为 光对组织的穿透性差，以及来自内源发色团的高背景信号。这个 电磁频谱的短波红外(SWIR)区域已成为 由于组织对光的散射减少和内源性最小的自体荧光而导致的光学成像 这一地区的生物分子。SWIR的潜力已经通过碳纳米管和 量子点作为造影剂；然而，关于这些材料的毒性问题阻碍了它们的临床应用 翻译。需要的是明亮、无毒的短波红外荧光团。 最近，我们报道了一种明亮的多亚甲基荧光团，被认为是Fram7，它可以吸收和释放 短波红外光。我们将把这种令人兴奋的第一代化合物转化为水-- 可添加到靶向剂和感兴趣的生物分子中的可溶性造影剂。我们会改进的 通过合成氟溶变异体制备Flaf7的纳米材料制剂。同时，我们将修改 该发色团结构可增强光物理性质并获得可 同时用于多路传输的SWIR成像。最后，我们将开发SWIR猝灭器，它将 使用蛋白酶可切割的肽序列连接到荧光团，以访问SWIR响应探针。 响应灵敏的探头提供了增强的信噪比，并且无需等待荧光团 安全。类似的响应探针的可见光和近红外版本目前正在进行成像- 有指导的手术。总体而言，我们的荧光体开发工作将为术中 成像、基于荧光内窥镜的诊断和光学乳房X光摄影。

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.