Chemiluminescent Probe for the In Vitro and In Vivo Imaging of Cancers Over-Expressing NQO1

Subin Son; Miae Won; Ori Green; Nir Hananya; Amit Sharma; Yukyoung Jeon; Jong Hwan Kwak; Jonathan L. Sessler; Doron Shabat; Jong Seung Kim

doi:10.1002/anie.201813032

Chemiluminescent Probe for the In Vitro and In Vivo Imaging of Cancers Over-Expressing NQO1

Subin Son, Miae Won, Ori Green, Nir Hananya, Amit Sharma, Yukyoung Jeon, Jong Hwan Kwak, Jonathan L. Sessler, Doron Shabat, Jong Seung Kim

Research output: Contribution to journal › Article › peer-review

75 Citations (Scopus)

Abstract

Activatable (turn-on) probes that permit the rapid, sensitive, selective, and accurate identification of cancer-associated biomarkers can help drive advances in cancer research. Herein, a NAD(P)H:quinone oxidoreductase-1 (NQO1)-specific chemiluminescent probe 1 is reported that allows the differentiation between cancer subtypes. Probe 1 incorporates an NQO1-specific trimethyl-locked quinone trigger moiety covalently tethered to a phenoxy-dioxetane moiety through a para-aminobenzyl alcohol linker. Bio-reduction of the quinone to the corresponding hydroquinone results in a chemiluminescent signal. As inferred from a combination of in vitro cell culture analyses and in vivo mice studies, the probe is safe, cell permeable, and capable of producing a “turn-on” luminescence response in an NQO1-positive A549 lung cancer model. On this basis, probe 1 can be used to identify cancerous cells and tissues characterized by elevated NQO1 levels.

Original language	English
Pages (from-to)	1739-1743
Number of pages	5
Journal	Angewandte Chemie - International Edition
Volume	58
Issue number	6
DOIs	https://doi.org/10.1002/anie.201813032
Publication status	Published - 2019 Feb 4

Keywords

NQO1
chemiluminescence
in vivo imaging
molecular probe

ASJC Scopus subject areas

Catalysis
Chemistry(all)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/anie.201813032

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title = "Chemiluminescent Probe for the In Vitro and In Vivo Imaging of Cancers Over-Expressing NQO1",

abstract = "Activatable (turn-on) probes that permit the rapid, sensitive, selective, and accurate identification of cancer-associated biomarkers can help drive advances in cancer research. Herein, a NAD(P)H:quinone oxidoreductase-1 (NQO1)-specific chemiluminescent probe 1 is reported that allows the differentiation between cancer subtypes. Probe 1 incorporates an NQO1-specific trimethyl-locked quinone trigger moiety covalently tethered to a phenoxy-dioxetane moiety through a para-aminobenzyl alcohol linker. Bio-reduction of the quinone to the corresponding hydroquinone results in a chemiluminescent signal. As inferred from a combination of in vitro cell culture analyses and in vivo mice studies, the probe is safe, cell permeable, and capable of producing a “turn-on” luminescence response in an NQO1-positive A549 lung cancer model. On this basis, probe 1 can be used to identify cancerous cells and tissues characterized by elevated NQO1 levels.",

keywords = "NQO1, chemiluminescence, in vivo imaging, molecular probe",

author = "Subin Son and Miae Won and Ori Green and Nir Hananya and Amit Sharma and Yukyoung Jeon and Kwak, {Jong Hwan} and Sessler, {Jonathan L.} and Doron Shabat and Kim, {Jong Seung}",

note = "Funding Information: This work was supported by the CRI project (Grant No. 2018R1A3B1052702, J.S.K.) and the Basic Science Research Program (Grant No. 2017R1D1A1B03030062, M.W.) of NRF in Korea. Support from the NIH (grant GM103790A to J.L.S.) and the Robert A. Welch Foundation (F-0018 to J.L.S.) is also gratefully acknowledged. D.S. thanks the Israel Science Foundation (ISF), the Binational Science Foundation (BSF), and the German Israeli Foundation (GIF) for financial support. Publisher Copyright: {\textcopyright} 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim",

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doi = "10.1002/anie.201813032",

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AU - Son, Subin

AU - Won, Miae

AU - Green, Ori

AU - Hananya, Nir

AU - Sharma, Amit

AU - Jeon, Yukyoung

AU - Kwak, Jong Hwan

AU - Sessler, Jonathan L.

AU - Shabat, Doron

AU - Kim, Jong Seung

N1 - Funding Information: This work was supported by the CRI project (Grant No. 2018R1A3B1052702, J.S.K.) and the Basic Science Research Program (Grant No. 2017R1D1A1B03030062, M.W.) of NRF in Korea. Support from the NIH (grant GM103790A to J.L.S.) and the Robert A. Welch Foundation (F-0018 to J.L.S.) is also gratefully acknowledged. D.S. thanks the Israel Science Foundation (ISF), the Binational Science Foundation (BSF), and the German Israeli Foundation (GIF) for financial support. Publisher Copyright: © 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

PY - 2019/2/4

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N2 - Activatable (turn-on) probes that permit the rapid, sensitive, selective, and accurate identification of cancer-associated biomarkers can help drive advances in cancer research. Herein, a NAD(P)H:quinone oxidoreductase-1 (NQO1)-specific chemiluminescent probe 1 is reported that allows the differentiation between cancer subtypes. Probe 1 incorporates an NQO1-specific trimethyl-locked quinone trigger moiety covalently tethered to a phenoxy-dioxetane moiety through a para-aminobenzyl alcohol linker. Bio-reduction of the quinone to the corresponding hydroquinone results in a chemiluminescent signal. As inferred from a combination of in vitro cell culture analyses and in vivo mice studies, the probe is safe, cell permeable, and capable of producing a “turn-on” luminescence response in an NQO1-positive A549 lung cancer model. On this basis, probe 1 can be used to identify cancerous cells and tissues characterized by elevated NQO1 levels.

AB - Activatable (turn-on) probes that permit the rapid, sensitive, selective, and accurate identification of cancer-associated biomarkers can help drive advances in cancer research. Herein, a NAD(P)H:quinone oxidoreductase-1 (NQO1)-specific chemiluminescent probe 1 is reported that allows the differentiation between cancer subtypes. Probe 1 incorporates an NQO1-specific trimethyl-locked quinone trigger moiety covalently tethered to a phenoxy-dioxetane moiety through a para-aminobenzyl alcohol linker. Bio-reduction of the quinone to the corresponding hydroquinone results in a chemiluminescent signal. As inferred from a combination of in vitro cell culture analyses and in vivo mice studies, the probe is safe, cell permeable, and capable of producing a “turn-on” luminescence response in an NQO1-positive A549 lung cancer model. On this basis, probe 1 can be used to identify cancerous cells and tissues characterized by elevated NQO1 levels.

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JO - Angewandte Chemie - International Edition

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ER -

Chemiluminescent Probe for the In Vitro and In Vivo Imaging of Cancers Over-Expressing NQO1

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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