Design and Synthesis of Novel Near-Infrared Fluorescence Probes Based on an Open Conformation of a Cytochrome P450 1B1 Complex for Molecular Imaging of Colorectal Tumors

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.