Bioluminescence Imaging of Carbon Monoxide in Living Cells and Nude Mice Based on Pd-0-Mediated Tsuji-Trost Reaction
Bioluminescence Imaging of Carbon Monoxide in Living Cells and Nude Mice Based on Pd-0-Mediated Tsuji-Trost Reaction
复制标题
基于 Pd-0 介导的 Tsuji-Trost 反应的活细胞和裸鼠中一氧化碳的生物发光成像
DOI：
10.1021/acs.analchem.8b01102
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发表时间：
2018
影响因子：
7.4
通讯作者：
Lu Jianzhong
中科院分区：
文献类型：
--
作者：
Tian Xiaodong;Liu Xinda;Wang Anni;Lau Choiwan;Lu Jianzhong
一氧化碳（CO）对人和动物具有高度毒性和致命性，因为它与血红蛋白具有很强的亲和力，而这种“沉默的杀手”在各种病理和生理条件下作为气体递质家族的细胞信号分子在体内不断产生。到目前为止，由于背景干扰、光散射和光活化/光漂白，设计用于活物种中CO实时成像的荧光探针是一个持续的挑战。本文合成了一种新型的生物荧光探针烯丙基-胡萝卜素，并利用其实现了高信噪比的CO成像。基于Pd 0介导的Tsuji-Trost反应，烯丙基-甜菜碱特异性地与CO反应生成D-甜菜碱，从而产生开启生物发光响应，对活性氮、氧和硫物种等生物活性小分子表现出高选择性。该探针可用于检测Huh 7细胞和MDA-MB-231细胞中外源性CO的生成，经[Ru（CO）3Cl-（glycinate）]（CORM-3）预处理后，细胞中CO的生成量显著增加。通过使用含PdCl 2的脂质体来改善PdCl 2的差的膜通透性，还清楚地看到血红素刺激的内源性CO。此外，该探针已成功地用于监测裸鼠体内外源性和内源性CO。总的来说，我们的数据证明，烯丙基甜菜碱是一个有前途的工具，外源性和内源性CO检测和成像活物种。这是第一次演示的生物发光成像所获得的CO探针。我们预计，在这项研究中提出的烯丙基-甜菜碱良好的成像性能将提供一个潜在的强大的方法，在未来照亮CO功能。
Carbon monoxide (CO) is highly toxic and lethal to humans and animals because of its strong affinity for hemoglobin, while this “silent killer” is constantly generated in the body as a cell-signaling molecule of the gasotransmitter family in various pathological and physiological conditions. Up to now, designing fluorescent probes for real-time imaging of CO in living species is a continuous challenge due to background interference, light scattering, and photoactivation/photobleaching. Herein, a novel type of bioluminescence probe (allyl-luciferin) was synthesized and exploited to realize CO imaging with high signal-to-noise ratios. Based on Pd0-mediated Tsuji–Trost reaction, allyl-luciferin specifically reacted with CO to yield D-luciferin and thus generate a turn-on bioluminescence response, exhibiting high selectivity against bioactive small molecules such as reactive nitrogen, oxygen, and sulfur species. Furthermore, the new probe can be easily employed to detect exogenous CO in Huh7 cells and MDA-MB-231 cells, and CO production was enhanced greatly in these living cells after pretreatment with [Ru(CO)3Cl-(glycinate)] (CORM-3). Through the use of PdCl2-containing liposomes to improve poor membrane permeability of PdCl2, endogenous CO stimulated by heme was also seen clearly. In addition, the probe was successfully used to monitor exogenous and endogenous CO in nude mice. Overall, our data proved that the allyl-luciferin is a promising tool for exogenous and endogenous CO detection and imaging within living species. This is the first demonstration of bioluminescence imaging obtained by a probe for CO. We anticipate that the good imaging properties of allyl-luciferin presented in this study will provide a potentially powerful approach for illuminating CO functions in the future.