量子传感器可通过电子顺磁共振、磁共振成像和光学成像来追踪细胞和组织中的总氧化还原状态和氧化应激。

Quantum Sensors To Track Total Redox-Status and Oxidative Stress in Cells and Tissues Using Electron-Paramagnetic Resonance, Magnetic Resonance Imaging, and Optical Imaging.

机构信息

Faculty of Medicine, Sofia University "St. Kliment Ohridski", 1 Koziak Str., Sofia 1407, Bulgaria.

Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, 21 Acad. G. Bonchev Str., Sofia 1113, Bulgaria.

出版信息

Anal Chem. 2021 Feb 9;93(5):2828-2837. doi: 10.1021/acs.analchem.0c04116. Epub 2021 Jan 28.

Abstract

Total redox capacity (TRC) and oxidative stress (OxiStress) of biological objects (such as cells, tissues, and body fluids) are some of the most frequently analyzed parameters in life science. Development of highly sensitive molecular probes and analytical methods for detection of these parameters is a rapidly growing sector of BioTech's R&D industry. The aim of the present study was to develop quantum sensors for tracking the TRC and/or OxiStress in living biological objects using electron-paramagnetic resonance (EPR), magnetic resonance imaging (MRI), and optical imaging. We describe a two-set sensor system: (i) TRC sensor QD@CD-TEMPO and (ii) OxiStress sensor QD@CD-TEMPOH. Both redox sensors are composed of small-size quantum dots (QDs), coated with multinitroxide-functionalized cyclodextrin (paramagnetic CD-TEMPO or diamagnetic CD-TEMPOH) conjugated with triphenylphosphonium (TPP) groups. The TPP groups were added to achieve intracellular delivery and mitochondrial localization. Nitroxide residues interact simultaneously with various oxidizers and reducers, and the sensors are transformed from the paramagnetic radical form (QD@CD-TEMPO) into diamagnetic hydroxylamine form (QD@CD-TEMPOH) and vice-versa, because of nitroxide redox-cycling. These chemical transformations are accompanied by characteristic dynamics of their contrast features because of quenching of QD fluorescence by nitroxide radicals. The TRC sensor was applied for EPR analysis of cellular redox-status in vitro on isolated cells with different proliferative indexes, as well as for noninvasive MRI of redox imbalance and severe oxidative stress in vivo on mice with renal dysfunction.

摘要

生物物体(如细胞、组织和体液)的总氧化还原容量(TRC)和氧化应激(OxiStress)是生命科学中经常分析的参数之一。开发用于检测这些参数的高灵敏度分子探针和分析方法是生物科技研发行业快速增长的领域。本研究的目的是开发量子传感器,使用电子顺磁共振(EPR)、磁共振成像(MRI)和光学成像来跟踪活生物物体中的 TRC 和/或 OxiStress。我们描述了一个由两部分组成的传感器系统:(i)TRC 传感器 QD@CD-TEMPO 和(ii)OxiStress 传感器 QD@CD-TEMPOH。这两种氧化还原传感器都由小尺寸量子点(QDs)组成,表面涂有多硝基功能化环糊精(顺磁性 CD-TEMPO 或反磁性 CD-TEMPOH),并与三苯基膦(TPP)基团结合。TPP 基团的添加是为了实现细胞内传递和线粒体定位。氮氧自由基同时与各种氧化剂和还原剂相互作用,由于氮氧自由基的氧化还原循环,传感器从顺磁自由基形式(QD@CD-TEMPO)转变为反磁羟胺形式(QD@CD-TEMPOH),反之亦然。这些化学转化伴随着其对比特征的特征动力学,因为氮氧自由基猝灭了 QD 荧光。TRC 传感器用于体外分离细胞的细胞氧化还原状态的 EPR 分析,以及用于肾功能障碍小鼠体内氧化失衡和严重氧化应激的非侵入性 MRI 分析。

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