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.

• Authors: Subin Son, Miae Won, Ori Green, Nir Hananya, Amit Sharma, Yukyoung Jeon, Jong Hwan Kwak, Jonathan L Sessler, Doron Shabat, Jong Seung Kim
• Journal: Angewandte Chemie (International ed. in English) (Angew Chem Int Ed Engl) Vol. 58 Issue 6 Pg. 1739-1743 (02 04 2019) ISSN: 1521-3773 [Electronic] Germany
• PMID: 30561862 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Benzoquinones
• Biomarkers, Tumor
• Fluorescent Dyes
• quinone
• NAD(P)H Dehydrogenase (Quinone)
• NQO1 protein, human

Topics

• A549 Cells
• Animals
• Benzoquinones (chemistry)
• Biomarkers, Tumor (chemistry, genetics, metabolism)
• Fluorescent Dyes (chemistry)
• Humans
• Luminescent Measurements
• Lung Neoplasms (diagnostic imaging, metabolism)
• Mice
• Molecular Structure
• NAD(P)H Dehydrogenase (Quinone) (chemistry, genetics, metabolism)
• Neoplasms, Experimental (diagnostic imaging, metabolism)
• Optical Imaging
• Tumor Cells, Cultured