title: Mitochondria Targeted and Intracellular Biothiol Triggered Hyperpolarized129Xe Magnetofluorescent Biosensor.
abstract: Biothiols such as gluthathione (GSH), cysteine (Cys), homocysteine (Hcy), and thioredoxin (Trx) play vital roles in cellular metabolism. Various diseases are associated with abnormal cellular biothiol levels. Thus, the intracellular detection of biothiol levels could be a useful diagnostic tool. A number of methods have been developed to detect intracellular thiols, but sensitivity and specificity problems have limited their applications. To address these limitations, we have designed a new biosensor based on hyperpolarized xenon magnetic resonance detection, which can be used to detect biothiol levels noninvasively. The biosensor is a multimodal probe that incorporates a cryptophane-A cage as129Xe NMR reporter, a naphthalimide moiety as fluorescence reporter, a disulfide bond as thiol-specific cleavable group, and a triphenylphosphonium moiety as mitochondria targeting unit. When the biosensor interacts with biothiols, disulfide bond cleavage leads to enhancements in the fluorescence intensity and changes in the129Xe chemical shift. Using Hyper-CEST (chemical exchange saturation transfer) NMR, our biosensor shows a low detection limit at picomolar (10-10M) concentration, which makes a promise to detect thiols in cells. The biosensor can detect biothiol effectively in live cells and shows good targeting ability to the mitochondria. This new approach not only offers a practical technique to detect thiols in live cells, but may also present an excellent in vivo test platform for xenon biosensors.
authors.affiliation: Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Collaborative Innovation Center of Chemistry for Life Sciences, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences , Wuhan 430071, People's Republic of China.|University of Chinese Academy of Sciences , Beijing 100049, People's Republic of China.
authors.forename: Qingbin
authors.initials: Q
authors.lastname: Zeng
authors.affiliation: Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Collaborative Innovation Center of Chemistry for Life Sciences, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences , Wuhan 430071, People's Republic of China.|University of Chinese Academy of Sciences , Beijing 100049, People's Republic of China.
authors.forename: Qianni
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Collaborative Innovation Center of Chemistry for Life Sciences, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences , Wuhan 430071, People's Republic of China.|University of Chinese Academy of Sciences , Beijing 100049, People's Republic of China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Collaborative Innovation Center of Chemistry for Life Sciences, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences , Wuhan 430071, People's Republic of China.
authors.forename: Yuqi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Collaborative Innovation Center of Chemistry for Life Sciences, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences , Wuhan 430071, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Collaborative Innovation Center of Chemistry for Life Sciences, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences , Wuhan 430071, People's Republic of China.
authors.forename: Lili
authors.initials: L
authors.lastname: Ren
authors.affiliation: Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Collaborative Innovation Center of Chemistry for Life Sciences, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences , Wuhan 430071, People's Republic of China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Collaborative Innovation Center of Chemistry for Life Sciences, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences , Wuhan 430071, People's Republic of China.|University of Chinese Academy of Sciences , Beijing 100049, People's Republic of China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Luo
authors.affiliation: Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Collaborative Innovation Center of Chemistry for Life Sciences, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences , Wuhan 430071, People's Republic of China.|University of Chinese Academy of Sciences , Beijing 100049, People's Republic of China.
authors.forename: Maili
authors.initials: M
authors.lastname: Liu
authors.affiliation: California Nano Systems Institute, Jonsson Comprehensive Cancer Center, The Molecular Biology Institute, Departments of Chemistry and Biochemistry and of Bioengineering, University of California , Los Angeles California 90095, United States.
authors.forename: Louis-S
authors.initials: LS
authors.lastname: Bouchard
authors.affiliation: Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Collaborative Innovation Center of Chemistry for Life Sciences, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences , Wuhan 430071, People's Republic of China.|University of Chinese Academy of Sciences , Beijing 100049, People's Republic of China.
authors.forename: Xin
authors.identifier: 0000-0002-5580-7907
authors.initials: X
authors.lastname: Zhou
mesh_terms: D015374:Biosensing Techniques / Q000379:methods*; D045744:Cell Line, Tumor; D003545:Cysteine / Q000032:analysis* / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry; D005978:Glutathione / Q000032:analysis* / Q000737:chemistry; D006710:Homocysteine / Q000032:analysis* / Q000737:chemistry; D006801:Humans; D057230:Limit of Detection; D009682:Magnetic Resonance Spectroscopy; D008280:Magnetics; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism*; D013879:Thioredoxins / Q000032:analysis* / Q000737:chemistry; D014979:Xenon Isotopes / Q000737:chemistry*
chemical_list: D005456:Fluorescent Dyes; D014979:Xenon Isotopes; C000614971:Xenon-129; D006710:Homocysteine; D013879:Thioredoxins; D005978:Glutathione; D003545:Cysteine