Biothiol-activatable bioluminescent coelenterazine derivative for molecular imaging in vitro and in vivo

Nanako Nomura, Ryo Nishihara, Takahiro Nakajima, Sung Bae Kim, Naoko Iwasawa, Yuki Hiruta, Shigeru Nishiyama, Moritoshi Sato, Daniel Citterio, Koji Suzuki

Research output: Contribution to journalArticle

Abstract

There is a high demand for sensitive biothiol probes targeting cysteine, glutathione, and homocysteine. These biothiols are known as playing essential roles to maintain homeostasis and work as indicators of many diseases. This work presents a bioluminescent probe (named AMCM) to detect biothiols in live mammalian cells and in vivo with a limit of detection of 0.11 μM for cysteine in solution and high selectivity for biothiols, making it suitable for real-time biothiol detection in biological systems. Upon application to live cells, AMCM showed low cytotoxicity and sensitively reported bioluminescence in response to changes of biothiol levels. Furthermore, a bioluminescence resonance energy transfer system consisting of AMCM combined with the near-infrared fluorescent protein iRFP713 was applied to in vivo imaging, with emitted tissue-permeable luminescence in living mice. In summary, this work demonstrates that AMCM is of high practical value for the detection of biothiols in living cells and for deep tissue imaging in living animals.

Original languageEnglish
Pages (from-to)9546-9553
Number of pages8
JournalAnalytical chemistry
Volume91
Issue number15
DOIs
Publication statusPublished - 2019 Aug 6

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Bioluminescence
Molecular imaging
Cysteine
Cells
Tissue
Derivatives
Imaging techniques
Homocysteine
Biological systems
Cytotoxicity
Energy transfer
Glutathione
Luminescence
Animals
Infrared radiation
Proteins
coelenterazine

ASJC Scopus subject areas

  • Analytical Chemistry

Cite this

Biothiol-activatable bioluminescent coelenterazine derivative for molecular imaging in vitro and in vivo. / Nomura, Nanako; Nishihara, Ryo; Nakajima, Takahiro; Kim, Sung Bae; Iwasawa, Naoko; Hiruta, Yuki; Nishiyama, Shigeru; Sato, Moritoshi; Citterio, Daniel; Suzuki, Koji.

In: Analytical chemistry, Vol. 91, No. 15, 06.08.2019, p. 9546-9553.

Research output: Contribution to journalArticle

Nomura, N, Nishihara, R, Nakajima, T, Kim, SB, Iwasawa, N, Hiruta, Y, Nishiyama, S, Sato, M, Citterio, D & Suzuki, K 2019, 'Biothiol-activatable bioluminescent coelenterazine derivative for molecular imaging in vitro and in vivo', Analytical chemistry, vol. 91, no. 15, pp. 9546-9553. https://doi.org/10.1021/acs.analchem.9b00694
Nomura, Nanako ; Nishihara, Ryo ; Nakajima, Takahiro ; Kim, Sung Bae ; Iwasawa, Naoko ; Hiruta, Yuki ; Nishiyama, Shigeru ; Sato, Moritoshi ; Citterio, Daniel ; Suzuki, Koji. / Biothiol-activatable bioluminescent coelenterazine derivative for molecular imaging in vitro and in vivo. In: Analytical chemistry. 2019 ; Vol. 91, No. 15. pp. 9546-9553.
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AU - Iwasawa, Naoko

AU - Hiruta, Yuki

AU - Nishiyama, Shigeru

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