前哨淋巴结（SLN）转移是乳腺癌远处转移的重要促进因素。因此，对患者分期和预后而言，及时的诊断和精确的治疗至关重要。然而，同时诊断转移和实施成像引导下的SLN治疗是具有挑战性的。在这里，我们报道了一种负载蜂毒素和透明质酸（HA）结合的高密度脂蛋白（HDL）类磷脂支架纳米颗粒（MLT-HA-HPPS），其双重靶向乳腺癌及其SLN，并在LN转移模型中有效抑制SLN转移。蜂毒素肽通过静电相互作用成功加载到HA-HPPS上，而MLT-HA-HPPS对乳腺癌4T1细胞具有有效的细胞毒性。此外，通过近红外荧光成像监测MLT-HA-HPPS从原发肿瘤进入SLN的有效传递，这对于转移性SLN的预后和治疗非常有益。经过癌旁给药后，MLT-HA-HPPS可以有效抑制原发肿瘤的生长，其抑制率相对于PBS处理对照组和HA-HPPS组分别为81.3%和76.5%。更重要的是，MLT-HA-HPPS能够有效抑制转移性SLN的生长，相对于PBS、HA-HPPS和蜂毒素处理的小鼠，其SLN重量减少了大约78.0%、79.1%和64.2%。综上所述，MLT-HA-HPPS可能提供一种鼓舞人心的SLN药物传递策略，用于抑制原发肿瘤进展和预防乳腺癌SLN转移。© 2023.作者。

Sentinel lymph node (SLN) metastasis is an important promoter of distant metastasis in breast cancer. Therefore, the timely diagnosis and precise treatment are crucial for patient staging and prognosis. However, the simultaneous diagnosis of metastasis and the implementation of imaging-guided SLN therapy is challenging. Here, we report a melittin-loaded and hyaluronic acid (HA)-conjugated high-density lipoprotein (HDL) mimic phospholipid scaffold nanoparticle (MLT-HA-HPPS), which dually-target to both breast cancer and its SLN and efficiently inhibit SLN metastasis in the LN metastasis model. The melittin peptide was successfully loaded onto HA-HPPS via electrostatic interactions, and MLT-HA-HPPS possesses effective cytotoxicity for breast cancer 4T1 cells. Moreover, the effective delivery of MLT-HA-HPPS from the primary tumor into SLN is monitored by NIR fluorescence imaging, which greatly benefits the prognosis and treatment of metastatic SLNs. After paracancerous administration, MLT-HA-HPPS can efficiently inhibit primary tumor growth with an inhibition rate of 81.3% and 76.5% relative to the PBS-treated control group and HA-HPPS group, respectively. More importantly, MLT-HA-HPPS can effectively inhibit the growth of the metastatic SLNs with an approximately 78.0%, 79.1%, and 64.2% decrease in SLNs weight than those in PBS, HA-HPPS, and melittin-treated mice, respectively. Taken together, the MLT-HA-HPPS may provide an encouraging theranostic of SLN drug delivery strategy to inhibit primary tumor progression and prevent SLN metastasis of breast cancer.© 2023. The Author(s).