Photoacoustic (PA) imaging is an emerging imaging modality that utilizes optical excitation and acoustic detection to enable high resolution at centimeter depths. The development of activatable PA probes can expand the utility of this technology to allow for detection of specific stimuli within live-animal models. Herein, we report the design, development, and evaluation of a series of Acoustogenic Probe(s) for Nitric Oxide (APNO) for the ratiometric, analyte-specific detection of nitric oxide (NO) in vivo. The best probe in the series, APNO-5, rapidly responds to NO to form an N-nitroso product with a concomitant 91 nm hypsochromic shift. This property enables ratiometric PA imaging upon selective irradiation of APNO-5 and the corresponding product, tAPNO-5. Moreover, APNO-5 displays the requisite photophysical characteristics for in vivo PA imaging (e.g., high absorptivity, low quantum yield) as well as high biocompatibility, stability, and selectivity for NO over a variety of biologically relevant analytes. APNO-5 was successfully applied to the detection of endogenous NO in a murine lipopolysaccharide-induced inflammation model. Our studies show a 1.9-fold increase in PA signal at 680 nm and a 1.3-fold ratiometric turn-on relative to a saline control.

中文翻译：

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用于内源性一氧化氮体内成像的比例声学探头

光声 (PA) 成像是一种新兴的成像方式，它利用光学激发和声学检测来实现厘米深度的高分辨率。可激活 PA 探针的开发可以扩展该技术的实用性，以检测活体动物模型中的特定刺激。在此，我们报告了一系列一氧化氮 (APNO) 声学探针的设计、开发和评估，用于体内一氧化氮 (NO) 的比例式、分析物特异性检测。该系列中最好的探针 APNO-5 可快速响应 NO，形成 N-亚硝基产物，并伴随 91 nm 的低色移。这一特性使得选择性照射 APNO-5 和相应产品 tAPNO-5 时能够进行比率 PA 成像。此外，APNO-5 显示了体内 PA 成像所需的光物理特性（例如，高吸收率、低量子产率）以及对 NO 相对于各种生物相关分析物的高生物相容性、稳定性和选择性。APNO-5 已成功应用于小鼠脂多糖诱导的炎症模型中内源性 NO 的检测。我们的研究表明，与盐水对照相比，680 nm 处的 PA 信号增加了 1.9 倍，比率开启增加了 1.3 倍。