한빛사 논문
고려대학교
Subin Sona,†, Miae Wona,†, Ori Greenb,†, Nir Hananyab,†, Amit Sharmaa, Yukyoung Jeonc, Jong Hwan Kwakc,*, Jonathan L Sesslerd,e,*, Doron Shabatb,*, Jong Seung Kima,*
aDepartment of Chemistry, Korea University, Seoul 02841, Korea.
bSchool of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
cSchool of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea
dCenter for Supramolecular Chemistry and Catalysis, Shanghai University, Shanghai 200444, China
eDepartment of Chemistry, University of Texas at Austin, Austin, Texas 78712-1224, U. S.
†These authors contributed equally to this work.
*To whom correspondence should be addressed.
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. Here we report a smart novel NAD(P)H:quinone oxidoreductase‐1 (NQO1) specific chemiluminescent Probe 1 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. Bioreduction of the quinone to the corresponding hydroquinone initiates a series of steps, which result 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. No such signal output was observed in an NQO1‐negative H596 lung cancer model. On this basis we suggest that Probe 1 can be used to identify cancerous cells and tissues characterized by elevated NQO1 levels.
Keywords: Chemiluminescence, NQO1, Molecular probe, In vivo imaging
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