A self-assembled fluorescent contrast agent targeting XIAP for image-guided surgery of bladder cancer

Fluorescently labeled tumor-specific molecular imaging agents have been extensively utilized in clinical settings to improve endoscopic tumor identification and subsequent resection by distinguishing tumors from normal tissues. However, the specificity and sensitivity of these fluorescent contrast agents have consistently presented challenges in accurately identifying tumors. Herein, we developed an innovative peptide conjugated NIR fluorescence probe (SA-FCA) targeting X-linked inhibitor of apoptosis protein (XIAP), not only ingeniously improves the imaging specificity with the help of tumor selective cascade activation process, but also significantly enhances the accumulation and retention ability of fluorescent probes by forming nanostructures through unique in situ self-assembly, and ensures excellent optical stability, thus achieving high sensitivity imaging effect. On this basis, the performance of SA-FCA was also excellent in potential clinical applications. In a trial involving 338 tissue samples from bladder cancer patients, SA-FCA successfully distinguished malignant and benign specimens with a specificity of up to 97.96 % and sensitivity of up to 99.58 %. SA-FCA could clearly identify tumor boundaries as well as microtumors (∼1 mm in diameter) in human tumor-bearing bladders. Compared with previous fluorescent contrast agents, SA-FCA exhibited higher specificity for distinguishing inflammatory tissues, necrotic tissues from tumor tissue, making it an ideal candidate for precision diagnosis and imaging-guided surgery of bladder cancer. This innovative technology opens new roads for the diagnosis of cancer, with great potential for clinical translation.