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用于活细胞中超氧阴离子成像的次膦酸酯基生物发光探针的设计

Design of a phosphinate-based bioluminescent probe for superoxide radical anion imaging in living cells.

作者信息

Liu Xinda, Tian Xiaodong, Xu Xu, Lu Jianzhong

机构信息

School of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai, P. R. China.

School of Pharmacy, Fudan University, Shanghai, P. R. China.

出版信息

Luminescence. 2018 Sep;33(6):1101-1106. doi: 10.1002/bio.3515. Epub 2018 Jul 3.

Abstract

Superoxide radical anion (O ˙ ) as an important member of reactive oxygen species (ROS) plays a vital role both in physiology and pathology. Herein we designed and synthesized a novel phosphinate-based bioluminescence probe for O ˙ detection in living cells, which exhibited good sensitivity for capturing O ˙ at the nanomole level and high selectivity against other ROS. The probe was further found to be of low toxicity for living cells and was then successfully employed for sensing endogenous O ˙ by using phorbol-12-myristate-13-acetate (PMA) as a traditional O ˙ stimulator in Huh7 cells. Moreover, the increasing production and use of nanoparticles, has given rise to many concerns and debates among the public and scientific authorities regarding their safety and final fate in biological systems. Herein it was found that mondisperse polystyrene particles could stimulate O ˙ generation in Huh7 cells. Overall, the probe was demonstrated to have a great potential as a novel bioluminescent sensor for detecting O ˙ in living cells. To our knowledge, this is the first small-molecule phosphinate-based bioluminescence probe that will open up great opportunities for unlocking the mystery of O ˙ in human health and disease.

摘要

超氧阴离子自由基(O˙)作为活性氧(ROS)的重要成员,在生理和病理过程中都起着至关重要的作用。在此,我们设计并合成了一种新型的基于次膦酸酯的生物发光探针,用于检测活细胞中的O˙,该探针在纳摩尔水平对捕获O˙表现出良好的灵敏度,并且对其他ROS具有高选择性。进一步发现该探针对活细胞毒性较低,然后通过使用佛波醇-12-肉豆蔻酸酯-13-乙酸酯(PMA)作为Huh7细胞中传统的O˙刺激剂,成功用于检测内源性O˙。此外,纳米颗粒的生产和使用日益增加,引发了公众和科学界对其在生物系统中的安全性和最终归宿的诸多关注和争论。在此发现,单分散聚苯乙烯颗粒可刺激Huh7细胞中O˙的产生。总体而言,该探针被证明作为一种用于检测活细胞中O˙的新型生物发光传感器具有巨大潜力。据我们所知,这是首个基于次膦酸酯的小分子生物发光探针,将为揭开O˙在人类健康和疾病中的奥秘带来巨大机遇。

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