pH-Activatable Molecular Probe for COX-2 Imaging in Human Oral Squamous Carcinoma Cells and Patient-Derived Tissues

For developing a successful cancer therapeutic modality, the early precise detection of cancer cells in patient biopsies in oral squamous cell carcinoma (OSCC) is crucial. This could help researchers create new diagnostic and therapeutic tools and assist clinicians in recommending more effective treatment plans and improving patient survival. We have developed an SMPD, cyclooxygenase-2 (COX-2) targeting pH-activable fluorophore named <b>CNP</b>, combining a potent COX-2 inhibitor, celecoxib, linked to a naphthalimide fluorophore with an acidic microenvironment-responsive piperazine moiety for specific optical imaging of OSCC in cells and patient tissues. Compared to reference probe <b>RNP</b> lacking celecoxib, <b>CNP</b> selectively enters the COX-2 overexpressing oral cancer cells. Its acidity-responsive imaging response enhances selectivity over cancers with lower COX-2 expression levels and normal cells. Further, <b>CNP</b> is demonstrated in imaging OSCC cells in patient-derived biopsies. Thus, multifunctional <b>CNP</b> shows potential in exploring more reagents for fluorescence-based detection of OSCC cells in patient tissues with translational applications.