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

Abstract

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, <b>2a1</b>, 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 <b>2a1</b> 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 <b>2a1</b> as a COX-2 near infrared fluorescent probe for human cancer imaging in clinical settings.