Thermosensitive NIR-II fluorescence nanotracer for targeted detection of sentinel lymph nodes

Current tracers for sentinel lymph node (SLN) biopsy in breast cancer suffer from limitations including poor accumulation, short retention times, and background staining interference at the surgical site. To address these shortcomings, we developed a dual-functional thermoresponsive nanotracer based on PbS quantum dots functionalized with poly(N-isopropylacrylamide) (PNIPAM) and polymannose (M₅₀), termed PbS-PNIPAM/M₅₀, that integrates second near-infrared (NIR-II) fluorescence imaging for enhanced signal clarity, specificity, and duration. This nanotracer demonstrated a fluorescence quantum yield of 8.65% at 1345 nm under 750 nm excitation. In vitro assays confirmed its targeting of macrophages via CD206, and in vivo NIR-II imaging revealed targeted SLN accumulation through active targeting and thermoresponsive clustering, which reduces drainage to non-sentinel nodes. Furthermore, immunofluorescence analysis verified the colocalization of the nanotracers with CD206 within lymphatic sinuses. The combination of macrophage retention mediated by CD206 and thermal aggregation driven by PNIPAM established a refined strategy for SLN mapping. This approach improves the accuracy of breast cancer staging by minimizing unnecessary lymph node dissection, highlighting the clinical potential of PbS-PNIPAM/M₅₀ for oncological SLN navigation.