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首页> 外文期刊>Advanced Functional Materials >Developing a Bright NIR-Ⅱ Fluorophore with Fast Renal Excretion and Its Application in Molecular Imaging of Immune Checkpoint PD-L1
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Developing a Bright NIR-Ⅱ Fluorophore with Fast Renal Excretion and Its Application in Molecular Imaging of Immune Checkpoint PD-L1

机译：快速肾脏排泄的明亮NIR-Ⅱ荧光团的开发及其在免疫检查点PD-L1分子成像中的应用

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摘要

Fluorescence imaging in the second near-infrared (NIR-II) window holds impressive advantages of enhanced penetration depth and improved signal-to-noise ratio. Bright NIR-II fluorophores with renal excretion ability and low tissue accumulation are favorable for in vivo molecular imaging applications as they can render the target-mediated molecular imaging process easily distinguishable. Here, a probe (anti-PD-L1-BGP6) comprising a fluorophore (IR-BGP6) covalently bonded to the programmed cell death ligand-1 monoclonal antibody (PD-L1 mAb) for molecular imaging of immune checkpoint PD-L1 (a targeting site upregulated in various tumors for cancer imaging) in the NIR-II window is reported. Through molecular optimization, the bright NIR-II fluorophore IR-BGP6 with fast renal excretion (approximate to 91% excretion in general through urine within the first 10 h postinjection) is developed. The conjugate anti-PD-L1-BGP6 succeeds in profiling PD-L1 expression and realizes efficient noninvasive molecular imaging in vivo, achieving a tumor to normal tissue (TINT) signal ratio as high as approximate to 9.5. Compared with the NIR-II fluorophore with high nonspecific tissue accumulation, IR-BGP6 derived PD-L1 imaging significantly enhances the molecular imaging performance, serving as a strong tool for potentially studying underlying mechanism of immunotherapy. The work providesrationales to design renal-excreted NIR-II fluorophores and illustrate their advantages for in vivo molecular imaging.
机译：第二个近红外（NIR-II）窗口中的荧光成像具有令人印象深刻的优点，即可以增加穿透深度并改善信噪比。具有肾脏排泄能力和低组织积聚的明亮NIR-II荧光团对于体内分子成像应用非常有利，因为它们可使目标介导的分子成像过程易于区分。在这里，探针（抗PD-L1-BGP6）包含与编程的细胞死亡配体-1单克隆抗体（PD-L1 mAb）共价结合的荧光团（IR-BGP6），用于免疫检查点PD-L1（a在NIR-II窗口中报告了在各种肿瘤中上调的靶向位点以进行癌症成像）。通过分子优化，开发了具有快速肾脏排泄（一般在注射后10小时内通过尿排泄约91％）的明亮NIR-II荧光团IR-BGP6。结合物抗PD-L1-BGP6成功分析了PD-L1表达，并在体内实现了有效的非侵入性分子成像，从而使肿瘤与正常组织（TINT）的信号比高达9.5。与具有高非特异性组织积累的NIR-II荧光团相比，IR-BGP6衍生的PD-L1成像显着增强了分子成像性能，成为潜在研究免疫疗法潜在机制的有力工具。这项工作为设计肾脏分泌的NIR-II荧光团提供了依据，并说明了它们在体内分子成像中的优势。

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  • 来源
    《Advanced Functional Materials》 |2018年第50期|1804956.1-1804956.10|共10页
  • 作者

    Wan Hao; Ma Huilong; Zhu Shoujun; Wang FeiFei; Tian Ye; Ma Rui; Yang Qinglai; Hu Zhubin; Zhu Tong; Wang Weizhi; Ma Zhuoran; Zhang Mingxi; Zhong Yeteng; Sun Haitao; Liang Yongye; Dai Hongjie;

  • 作者单位

    Stanford Univ, Dept Chem, Stanford, CA 94305 USA;

    South Univ Sci & Technol China, Dept Mat Sci & Engn, Shenzhen 518055, Peoples R China;

    Stanford Univ, Dept Chem, Stanford, CA 94305 USA;

    Stanford Univ, Dept Chem, Stanford, CA 94305 USA;

    Stanford Univ, Dept Chem, Stanford, CA 94305 USA;

    South Univ Sci & Technol China, Dept Mat Sci & Engn, Shenzhen 518055, Peoples R China;

    South Univ Sci & Technol China, Dept Mat Sci & Engn, Shenzhen 518055, Peoples R China;

    East China Normal Univ, Sch Phys & Mat Sci, State Key Lab Precis Spect, Shanghai 200062, Peoples R China;

    East China Normal Univ, Sch Chem & Mol Engn, Shanghai 200062, Peoples R China;

    Stanford Univ, Dept Chem, Stanford, CA 94305 USA;

    Stanford Univ, Dept Chem, Stanford, CA 94305 USA;

    Stanford Univ, Dept Chem, Stanford, CA 94305 USA;

    Stanford Univ, Dept Chem, Stanford, CA 94305 USA;

    East China Normal Univ, Sch Phys & Mat Sci, State Key Lab Precis Spect, Shanghai 200062, Peoples R China|Shanxi Univ, Collaborat Innovat Ctr Extreme Opt, Taiyuan 030006, Shanxi, Peoples R China;

    South Univ Sci & Technol China, Dept Mat Sci & Engn, Shenzhen 518055, Peoples R China;

    Stanford Univ, Dept Chem, Stanford, CA 94305 USA;

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  • 正文语种 eng
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  • 关键词

    molecular imaging; NIR-II fluorophore; PD-L1; renal excretion;

    机译：分子成像;NIR-II荧光团;PD-L1;肾脏排泄;

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