Tumor metastasis remains the primary cause of treatment failure in cancer patients, and the high-sensitivity preoperative and intraoperative detection of occult micrometastases continues to pose a notorious challenge. Therefore, we have designed an in situ albumin-hitchhiking near-infrared window II (NIR-II) fluorescence probe, IR1080, for the precise detection of micrometastases and subsequent fluorescence image-guided surgery. IR1080 rapidly covalently conjugates with albumin in plasma, resulting in a stronger fluorescence brightness upon binding. Moreover, the albumin-hitchhiked IR1080 has a high affinity for secreted protein acidic and rich in cysteine (SPARC), an albumin-binding protein that is overexpressed in micrometastases. The interaction between SPARC and IR1080-hitchhiked albumin enhances IR1080's capacity to track and anchor micrometastases, leading to a high detection rate and margin delineation ability, as well as a high tumor-to-normal tissue ratio. Therefore, IR1080 represents a highly efficient strategy for the diagnosis and image-guided resection surgery of micrometastases.
Keywords: albumin-binding protein; in situ albumin-hitchhiking; micrometastases-seeking; second near-infrared window imaging; small-molecule fluorescent probe.