pH-Activatable Molecular\nProbe for COX‑2 Imaging\nin Human Oral Squamous Carcinoma Cells and Patient-Derived Tissues

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