Aromatic primary monoamine-based fast-response and highly specific fluorescent probes for imaging the biological signaling molecule nitric oxide in living cells and organisms.
Aromatic primary monoamine-based fast-response and highly specific fluorescent probes for imaging the biological signaling molecule nitric oxide in living cells and organisms.
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DOI：
10.1039/c6tb03382b
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发表时间：
2017-03
期刊：
影响因子：
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通讯作者：
Yingying Huo;Junfeng Miao;Yaping Li;Yawei Shi;Heping Shi;W. Guo
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文献类型：
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作者：
Yingying Huo;Junfeng Miao;Yaping Li;Yawei Shi;Heping Shi;W. Guo
一氧化氮（NO）是一种重要的细胞信号分子，参与多种生理和病理过程。为了探测NO在生物系统中的时空信息，近十年来，大量的NO荧光探针被开发出来。其中，邻苯二胺类荧光探针是迄今为止开发最早、用途最广的NO荧光探针。然而，仍然存在诸如相对较长的响应时间、脱氢抗坏血酸（DHA）/甲基乙二醛（MGO）的可能干扰以及它们的荧光信号的pH敏感性等限制。本工作中，我们提出了两种基于芳香伯单胺的NO荧光探针MA和NIR-MA，并探讨了富电子对甲氧基苯胺基团与NO在有氧条件下的还原脱氨反应。这两种探针的优越性说明了其快速，稳定，灵敏，特异性的荧光关-关响应NO在一系列的生物相关的干扰物种，包括活性氧，DHA/MGO，biothiols，和金属离子。结合良好的细胞渗透性和低细胞毒性，这两种探针已成功地应用于LPS/IFN-γ刺激的RAW 264.7巨噬细胞内源性NO的成像。此外，NIR-MA对NO的荧光响应发生在生理上有利的NIR区域，使其能够进一步用于在发炎小鼠模型中对内源性NO进行成像。
Nitric oxide (NO) is an important cellular signaling molecule involved in many physiological and pathological processes. To probe its spatiotemporal information in biosystems, a large number of NO fluorescent probes have been exploited in the past ten years. Among them, the o-phenylenediamine-based probes are the earliest developed and most versatile NO fluorescent probes to date. However, there are still limitations such as relatively long response time, possible interference by dehydroascorbic acid (DHA)/methylglyoxal (MGO), and pH-sensitivity of their fluorescence signals. In this work, we present two aromatic primary monoamine-based NO fluorescent probes, MA and NIR-MA, and explore the reductive deamination reaction of the electron-rich p-methoxyaniline group with NO under aerobic conditions. The superiority of both probes is illustrated by their quick, stable, sensitive, and specific fluorescence off-on responses for NO over a series of biologically relevant interfering species, including reactive oxygen species, DHA/MGO, biothiols, and metal ions. Coupled with good cell permeability and low cytotoxicity, the two probes have successfully been applied to imaging the endogenous NO in RAW 264.7 macrophages stimulated by LPS/IFN-γ. Moreover, the fluorescence response of NIR-MA for NO occurs in the physiologically favorable NIR region, enabling its further use to image endogenous NO in an inflamed mouse model.