Cytochrome P450 1B1 (CYP1B1) is induced during the early stage of
cancer and is universally overexpressed in
tumors. Thus, it was considered as a potential
biomarker for the monitoring of
cancer. In this study, we designed and synthesized CYP1B1-targeted near-infrared (NIR) fluorescence
molecular probes based on the latest reported open conformation of the CYP1B1-α-naphthoflavone (
ANF) complex. According to the architecture of the open channel, we introduced linkers and a
Cy5.5 fragment at the 5' position of
ANF derivatives with strong CYP1B1 inhibitory activity to obtain probes 19-21. Then, in vitro cell-based studies showed that the probes could be enriched in
tumor cells by binding to CYP1B1. During in vivo and ex vivo imaging in a xenograft mouse model, probe 19 with the best binding affinity was proven to be able to identify
tumor sites in both fluorescence imaging and photoacoustic imaging modes.