Real-time detection and resection of sentinel lymph node metastasis in breast cancer through a rare earth nanoprobe based NIR-IIb fluorescence imaging

Sentinel lymph node (SLN) biopsy is a commonly employed procedure for the routine assessment of axillary involvement in patients with breast cancer. Nevertheless, conventional SLN mapping cannot reliably distinguish the presence and absence of metastatic disease. Additionally, the complex anatomical structures and lymphatic drainage patterns surrounding tumor sites pose challenges to the sensitivity of the near-infrared fluorescence imaging with subcutaneously injected probes. To identifying the SLN metastases, we developed a novel nanoprobe for in vivo fluorescence imaging within the second near-infrared (NIR-II) range. This nanoprobe utilizes rare-earth nanoparticles (RENPs) to emit bright fluorescence at 1525 nm and is conjugated with tumor-targeted hyaluronic acid (HA) to facilitate the detection of metastatic SLN. Upon intravenous administration, RENPs@HA effectively migrated to SLNs and selectively entered metastatic breast tumor cells through CD44-mediated endocytosis. The RENPs@HA nanoprobes exhibited rapid accumulation in metastatic inguinal lymph nodes in mouse model, displaying a 5.8-fold-stronger fluorescence intensity to that observed in normal SLNs. Consequently, these nanoprobes effectively differentiate metastatic SLNs from normal SLNs. Importantly, the probes accurately detected micrometastases. These findings underscore the potential of RENPs@HA for real-time visualization and screening of SLNs metastasis.