Olympus Corporation , 2-3 Kuboyamacho , Hachioji-shi, Tokyo 192-8512 , Japan.
Japan Agency for Medical Research and Development , 1-7-1 Otemachi , Chiyoda-ku, Tokyo 100-0004 , Japan.
Anal Chem. 2019 Jul 16;91(14):9086-9092. doi: 10.1021/acs.analchem.9b01529. Epub 2019 Jul 2.
Photoacoustic (PA) imaging is a novel imaging modality that combines the high contrast of optical imaging and the deep tissue penetration of ultrasound. PA imaging contrast agents targeting various biological phenomena have been reported, but the development of activatable PA probes, which show a PA signal only in the presence of target molecules, remains challenging in spite of their potential usefulness for real-time PA imaging of specific biomolecules in vivo. To establish a simple design strategy for activatable PA probes, we first designed and synthesized a silicon-rhodamine based near-infrared nonfluorescent dye, wsSiNQ660 (water-soluble SiNQ660), as a scaffold and demonstrated that it offers a high conversion efficiency from light to ultrasound compared to typical near-infrared fluorescent dyes. Importantly, absorption off/on strategies previously established for rhodamine-based fluorescent probes are also applicable to this nonfluorescent dye scaffold. We validated this approach by synthesizing an activatable PA probe for hypochlorous acid (HOCl) and confirmed that it enables three-dimensional imaging of HOCl in mouse subcutis.
光声（PA）成像是一种结合了光学成像高对比度和超声深穿透能力的新型成像模式。已经有报道称针对各种生物现象的 PA 成像对比剂，但开发仅在存在靶分子的情况下才显示出 PA 信号的激活型 PA 探针仍然具有挑战性，尽管它们对于实时体内特定生物分子的 PA 成像具有潜在的用途。为了建立激活型 PA 探针的简单设计策略，我们首先设计并合成了一种基于硅罗丹明的近红外非荧光染料 wsSiNQ660（水溶性 SiNQ660），作为支架，并证明与典型的近红外荧光染料相比，它具有更高的光声转换效率。重要的是，先前为基于罗丹明的荧光探针建立的吸收开/关策略也适用于这种非荧光染料支架。我们通过合成用于次氯酸（HOCl）的激活型 PA 探针验证了这种方法，并证实它能够实现小鼠皮下组织中 HOCl 的三维成像。
