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线粒体靶向近红外荧光探针用于高识别率检测细胞内纳摩尔级别的硫化氢。

Mitochondrion-targeting near-infrared fluorescent probe for detecting intracellular nanomolar level hydrogen sulfide with high recognition rate.

机构信息

School of Chemical Sciences, University of Chinese Academy of Sciences (UCAS), Beijing, 100049, China.

出版信息

Anal Bioanal Chem. 2021 Feb;413(4):1215-1224. doi: 10.1007/s00216-020-03086-6. Epub 2021 Jan 2.

DOI:10.1007/s00216-020-03086-6
PMID:33386936
Abstract

Hydrogen sulfide (HS) typically plays biphasic biological roles in living organisms with subnormal HS exerting cytoprotective effects such as participating in cardioprotective signaling pathways while HS with higher-than-normal concentrations in localized tissues acting the opposite way such as inhibiting mitochondrial respiration. Such concentration-dependent biological and pathological roles of HS with the wide involvement of mitochondria and the elusive feature of HS definitely highlight the vital significance of fast and precise estimation of the physiological level of HS in specific microenvironments, particularly within cellular mitochondria. In this work, we developed a new type of fluorescent probe (QcyCHO) featured with HS-triggered off-to-on near-infrared (NIR) fluorescence conversion within ~ 10 min, limit of detection (LOD) down to 8.3 nM, and high recognition specificity over other similarly interfering species. The ideal mitochondrion-targeting ability, high recognition specificity over typical interfering substances and other physiologically relevant species, and the ability for mapping intracellular HS in living cells of QcyCHO probe were also unequivocally confirmed, which imply its potential for shedding light on the biology of HS and therapeutic development in HS-associated diseases by identifying the specific physiological stimuli inducing HS production and determining the levels of HS at the location and time of stimulation.

摘要

硫化氢 (HS) 通常在生物体中发挥双相生物学作用,正常水平以下的 HS 发挥细胞保护作用,如参与心脏保护信号通路,而局部组织中高于正常水平的 HS 则产生相反的作用,如抑制线粒体呼吸。HS 的这种浓度依赖性生物学和病理学作用广泛涉及线粒体,且 HS 的难以捉摸的特性突出了快速、准确估计特定微环境中 HS 生理水平的重要意义,特别是在细胞线粒体中。在这项工作中,我们开发了一种新型荧光探针 (QcyCHO),具有 HS 触发的近红外 (NIR) 荧光转换,在 10 分钟内从关闭到打开,检测限 (LOD) 低至 8.3 nM,对其他类似干扰物质具有很高的识别特异性。QcyCHO 探针还明确证实了其理想的线粒体靶向能力、对典型干扰物质和其他生理相关物质的高识别特异性,以及在活细胞内映射细胞内 HS 的能力,这意味着它有可能通过识别诱导 HS 产生的特定生理刺激,并确定刺激位置和时间的 HS 水平,为 HS 相关疾病的治疗发展提供依据,从而阐明 HS 的生物学。

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