Detection of sentinel lymph nodes (SLNs) is critical to guide the treatment of breast cancer. However, distinguishing metastatic SLNs from normal and inflamed lymph nodes (LNs) during surgical resection remains a challenge. Here, we report a CD44 and scavenger receptor class B1 dual-targeting hyaluronic acid nanoparticle (5K-HA-HPPS) loaded with the near-infra-red fluorescent dye DiR-BOA for SLN imaging in breast cancer. The small sized (~40 nm) self-assembled 5K-HA-HPPSs accumulated rapidly in the SLNs after intradermal injection. Compared with normal popliteal LNs (N-LN), there were ~3.2-fold and ~2.4-fold increases in fluorescence intensity in tumour metastatic SLNs (T-MLN) and inflamed LNs (Inf-LN), respectively, 6 h after nanoparticle inoculation. More importantly, photoacoustic microscopy (PAM) of 5K-HA-HPPS showed a significantly distinct distribution in T-MLN compared with N-LN and Inf-LN. Signals were mainly distributed at the centre of T-MLN but at the periphery of N-LN and Inf-LN. The ratio of PA intensity (R) at the centre of the LNs compared with that at the periphery was 5.93 ± 0.75 for T-MLNs of the 5K-HA-HPPS group, which was much higher than that for the Inf-LNs (R = 0.2 ± 0.07) and N-LNs (R = 0.45 ± 0.09). These results suggest that 5K-HA-HPPS injection combined with PAM provides a powerful tool for distinguishing metastatic SLNs from pLNs and inflamed LNs, thus guiding the removal of SLNs during breast cancer surgery.

前哨淋巴结（SLN）的检测对于指导乳腺癌的治疗至关重要。然而，在手术切除过程中区分转移性前哨淋巴结与正常和发炎的淋巴结 (LN) 仍然是一个挑战。在这里，我们报道了一种装载有近红外荧光染料 DiR-BOA 的 CD44 和 B1 类清道夫受体双靶向透明质酸纳米颗粒 (5K-HA-HPPS)，用于乳腺癌 SLN 成像。皮内注射后，小尺寸（约 40 nm）自组装 5K-HA-HPPS 在 SLN 中快速积累。与正常腘窝淋巴结 (N-LN) 相比，纳米粒子照射后 6 小时，肿瘤转移性淋巴结 (T-MLN) 和发炎淋巴结 (Inf-LN) 的荧光强度分别增加约 3.2 倍和约 2.4 倍接种。更重要的是，5K-HA-HPPS 的光声显微镜 (PAM) 显示，与 N-LN 和 Inf-LN 相比，T-MLN 中的分布显着不同。信号主要分布在T-MLN的中心，但分布在N-LN和Inf-LN的外围。5K-HA-HPPS 组 T-MLN 的 LN 中心与周边的 PA 强度（R）之比为 5.93 ± 0.75，远高于 Inf-LN（R  = 0.2 ± 0.07) 和 N-LN ( R  = 0.45 ± 0.09)。这些结果表明，5K-HA-HPPS注射结合PAM提供了区分转移性SLN、pLN和发炎LN的有力工具，从而指导乳腺癌手术期间SLN的去除。