A novel near-infrared COX-2 targeting probe for tumor and metastatic lymph node monitoring.

Intraoperative fluorescence-guided imaging has transformed oncological surgery, yet clinically approved probes lack specificity for primary tumors and metastatic lymph nodes. Herein, we developed NY-IND, a near-infrared fluorescent (NIRF) probe targeting cyclooxygenase-2 (COX-2). NY-IND not only has high water solubility, but also boasts higher fluorescence quantum yield and excellent biosafety. NY-IND exhibited high binding affinity for the COX-2 target with a dissociation constant (Kd) of 99.69 nM, thereby endowing it with the capacity to specifically recognize COX-2-overexpressing tumor cells and tissues. Significant tumor-to-background ratio (TBR > 6) was still observed 48 h after injection, allowing for clear differentiation between subcutaneous tumors and surrounding tissues. Furthermore, the probe NY-IND exhibited a long tumor retention time (>72 h) in vivo metabolism and provided a longer imaging window for fluorescence-guided tumor surgery. NY-IND showed significantly superior specificity in detecting metastatic tumor lesions including peritoneal metastasis of lung cancer and lymph node metastasis. This work presents a promising tool for real-time intraoperative visualization of tumors and metastases, advancing surgical precision and improving patient prognosis.