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


Journal

Angewandte Chemie (International ed. in English)
ISSN: 1521-3773
Titre abrégé: Angew Chem Int Ed Engl
Pays: Germany
ID NLM: 0370543

Informations de publication

Date de publication:
04 02 2019
Historique:
received: 14 11 2018
revised: 17 12 2018
pubmed: 19 12 2018
medline: 19 8 2020
entrez: 19 12 2018
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 30561862
doi: 10.1002/anie.201813032
doi:

Substances chimiques

Benzoquinones 0
Biomarkers, Tumor 0
Fluorescent Dyes 0
quinone 3T006GV98U
NAD(P)H Dehydrogenase (Quinone) EC 1.6.5.2
NQO1 protein, human EC 1.6.5.2

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1739-1743

Informations de copyright

© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Auteurs

Subin Son (S)

Department of Chemistry, Korea University, Seoul, 02841, Korea.

Miae Won (M)

Department of Chemistry, Korea University, Seoul, 02841, Korea.

Ori Green (O)

School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv, 69978, Israel.

Nir Hananya (N)

School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv, 69978, Israel.

Amit Sharma (A)

Department of Chemistry, Korea University, Seoul, 02841, Korea.

Yukyoung Jeon (Y)

School of Pharmacy, Sungkyunkwan University, Suwon, 16419, Korea.

Jong Hwan Kwak (JH)

School of Pharmacy, Sungkyunkwan University, Suwon, 16419, Korea.

Jonathan L Sessler (JL)

Center for Supramolecular Chemistry and Catalysis, Shanghai University, Shanghai, 200444, China.
Department of Chemistry, University of Texas at Austin, Austin, TX, 78712-1224, USA.

Doron Shabat (D)

School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv, 69978, Israel.

Jong Seung Kim (JS)

Department of Chemistry, Korea University, Seoul, 02841, Korea.

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Classifications MeSH