1. Joint Laboratory of Opto-Functional Theranostics in Medicine and Chemistry, The First Hospital of Jilin University, Changchun 130021, China.
2. State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun 130012, China.
3. Department of Gastrointestinal Surgery, The First Hospital of Jilin University, Changchun 130021, China.
4. Department of Obstetrics and Gynecology, The First Hospital of Jilin University, Changchun, 130021, China.
5. Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and College of Design and Engineering, National University of Singapore, Singapore 119074, Singapore.
6. Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore.
7. Nanomedicine Translational Research Program, NUS Center for Nanomedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.
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 (I1060 nm/I1525 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.
Keywords: ratiometric fluorescence, non-invasive detection, identification of tumor-draining lymph nodes, sentinel lymph node, near-infrared-II imaging-guided surgery