Near-infrared-II ratiometric fluorescence probes for non-invasive detection and precise navigation surgery of metastatic sentinel lymph nodes

Sentinel lymph node (SLN) biopsy is the key diagnostic procedure to determine tumor metastasis and treatment plan. Current SLN biopsy has considerable drawbacks in that SLNs (both malignant and normal) must be removed by navigation surgery, followed by a time-consuming pathological examination. The selective, non-invasive, and real-time diagnosis of metastatic status in SLNs is becoming essential. Methods: Here, we design two lanthanide-doped nanoparticles as a pair of NIR-II ratiometric fluorescence probes, one of which is conjugated with tumor-targeting moiety, while the other is conjugated with PEG as an internal reference. The NIR-II ratiometric fluorescence signal (I(1060 nm)/I(1525 nm)) from two well-separated channels were used to identify the tumor-draining SLNs. The precise navigation surgery of metastatic SLNs was performed and we further evaluated their surgery outcomes. Results: The NIR-II ratiometric fluorescence facilitates an ideal fluorescence-guided surgery with only resection of tumor-positive SLNs, thereby avoiding unnecessary removal of the normal SLNs. In addition, our system has a time-saving operation procedure and can be performed under the operation light without altering the appearance of surgical settings. Conclusion: The present study enables non-invasive and real-time detection metastatic status in SLNs with high sensitivity and selectivity. Our investigations will provide a new direction for SLN biopsy and substantially improve cancer surgery outcomes.