One-Step Transformation from Rofecoxib to a COX-2 NIR Probe for Human Cancer Tissue/Organoid Targeted Bioimaging

COX-2 fluorescent probes are promising tools for cancer diagnosis. Such probes have been conventionally designed by conjugating a fluorophore to COX-2 inhibitors through lengthy synthetic processes. Herein, a type of fluorescent probe for COX-2 imaging has been developed using a single-step process from rofecoxib. In total, six rofecoxib analogues were designed using this unique strategy. Several analogues retained comparative COX-2 targeting activity of rofecoxib and also exhibited attractive fluorescent properties, which were investigated using a combination of experimental and theoretical approaches. The most potent analogue, 2a1, displayed strong fluorescent imaging of COX-2 in HeLa cells overexpressing COX-2 compared to Raw 264.7 cells and celecoxib-treated HeLa cells that expressed low levels of COX-2. Notably, our studies indicate that 2a1 can differentiate human cancer tissue from adjacent tissue with much brighter fluorescence either in histological section or cultured 3D organoids. These results illustrate the potential of 2a1 as a COX-2 near infrared fluorescent probe for human cancer imaging in clinical settings.

Automated summary

Fluorescent probes for COX-2 imaging have been developed using a single-step process from rofecoxib, showing potential for strong fluorescence imaging of COX-2 in human cancer tissue. The most potent analogue, 2a1, exhibited promising COX-2 targeting activity and attractive fluorescent properties, highlighting its potential as a near infrared fluorescent probe for human cancer imaging in clinical settings.