A Rofecoxib‐Derived Theranostic Probe and Its Combination With PD‐1 Inhibitor for High‐Efficiency Cancer Therapy

The development of theranostic probes with tumor-specific targeting and high therapeutic efficacy remains a pivotal challenge in precision oncology. Herein, we have successfully developed a new cyclooxygenase-2 (COX-2)-targeted probe compound 2 derived from Rofecoxib. Compound 2 facilitated tumor visualization by a sixfold fluorescence enhancement upon COX-2 binding, while it exhibited minimal background fluorescence under physiological conditions. Moreover, compound 2 monotherapy achieved 53% tumor regression (p < 0.01). When combined with a programmed cell death protein 1 (PD-1) inhibitor (RMP1-14), concurrent blockade of the COX-2/prostaglandin E2 (PGE2) and PD-1/programmed death-ligand 1 (PD-L1) axes achieved 95% tumor regression (p < 0.001). Compound 2 involves activating fluorescence by targeting tumor markers COX-2 as well as enhancing therapeutic efficacy. We believe this approach could provide insights for advancing cancer diagnosis and treatment technologies.