Chemiluminescent Probe for the InVitro and InVivo Imaging of Cancers Over-Expressing NQO1

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 probe1 is reported that allows the differentiation between cancer subtypes. Probe1 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 invitro cell culture analyses and invivo 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, probe1 can be used to identify cancerous cells and tissues characterized by elevated NQO1 levels.