Precise tumor delineation in clinical tissues using a novel acidic tumor microenvironment activatable near-infrared fluorescent contrast agent.

Tumor selective near-infrared (NIR) fluorescent contrast agents has the potential to greatly enhance the efficiency and precision of tumor surgery by enabling real-time tumor margin identification for tumor resection guided by imaging. However, the development of these agents is still challenging. In this study, based on the acidic tumor microenvironment (TME), we designed and synthesized a novel pH-sensitive NIR fluorescent contrast agent OBD from β-carboline. The fluorescence quantum yield of OBD exhibited a notable increase at pH 3.6, approximately 12-fold higher compared to its value at pH 7.4. After cellular uptake, OBD lighted up the cancer cells with high specificity and accumulated in the mitochondria. Spraying OBD emitted selective fluorescence in xenograft tumor tissues with tumor-to-normal tissue ratios (TNR) as high as 11.18, implying successful image-guided surgery. Furthermore, OBD was also shown to track metastasis in spray mode. After simple topical spray, OBD rapidly and precisely visualized the tumor margins of clinical colon and liver tissues with TNR over 4.2. Therefore, the small-molecule fluorescent contrast agent OBD has promising clinical applications in tumor identification during surgery. [Display omitted] • Fluorescent contrast agent OBD derived from β-carboline was rapidly activated under acidic TME. • The fluorescence quantum yield of OBD at pH 3.6 was 12-fold higher than pH 7.4. • OBD selectively lighted up cancer cells with tumor-to-normal fluorescent ratios of 4∼6. • OBD traced both xenograft and metastatic tumors to guide surgical resection in vivo. • OBD identified tumor margins of clinical colon/liver tissues after simple spray with TNR >4.2. [ABSTRACT FROM AUTHOR]