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Chemiluminescent Probe for the In Vitro and In Vivo Imaging of Cancers Over‐Expressing NQO1
Author(s) -
Son Subin,
Won Miae,
Green Ori,
Hananya Nir,
Sharma Amit,
Jeon Yukyoung,
Kwak Jong Hwan,
Sessler Jonathan L.,
Shabat Doron,
Kim Jong Seung
Publication year - 2019
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201813032
Subject(s) - moiety , chemiluminescence , in vivo , chemistry , hydroquinone , quinone , in vitro , linker , dioxetane , nad+ kinase , cancer cell , cancer , biochemistry , combinatorial chemistry , cancer research , biophysics , stereochemistry , biology , enzyme , organic chemistry , genetics , microbiology and biotechnology , computer science , operating system
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.