Intraoperative diagnosis of early lymphatic metastasis using neodymium-based rare-earth NIR-II fluorescence nanoprobe

Abstract

The high mortality of breast cancer is closely related to lymph node (LN) metastasis. Sentinel LNs (SLNs) are the first station where tumor cells metastasize through the lymphatic system. As such, achieving precise diagnosis of the early metastatic status of SLNs during surgery is of paramount importance for precision therapy of breast cancer. While invasive SLNs biopsy is the gold standard for evaluating the status of SLNs, its use is often time-consuming and may increase the risk of operation. It is still challenging to develop a means for rapid SLN metastasis diagnosis. Herein, NaGdF₄:5%Nd@NaLuF₄ rare earth nanoparticles (Gd:Nd-RENPs) with near-infrared-II (NIR-II) fluorescence and magnetic resonance imaging (MRI) properties were fabricated. With the nanoprobe, metastatic SLNs and lymph vessels (LVs) rapidly brighten and can be observed by the NIR-II imaging system, which is totally different from normal LNs and LVs. The remarkable contrast observed via NIR-II imaging serves to swiftly delineate metastatic SLNs from normal ones, subsequently guiding precise surgical resection of metastatic LNs in just 10 minutes. Furthermore, the consistency between the results obtained via MRI and NIR-II imaging further validates the dependability of this nanoprobe as a diagnostic tool for metastatic SLNs. Additionally, the Gd:Nd-RENPs exhibited good biocompatibility in vitro and in vivo. In this study, we demonstrated the advantages and prospects of NIR-II imaging for intraoperative early SLN metastasis assessment and shed light on the potential of the dual-modal Gd:Nd-RENPs as a nanoprobe.