前哨淋巴结（SLN）活检在乳腺癌腋窝分期中发挥着关键作用。然而，传统的SLN映射不能准确识别转移性疾病的存在或缺失。对SLN转移的检测在很大程度上依赖于SLN活检后冰冻切片或石蜡包埋组织的检查。为了改善SLN转移的检测，我们开发了一种第二近红外（NIR-II）体内荧光成像系统，将基于钇的稀土金属纳米颗粒（ErNPs）与1556 nm的明亮下转换荧光配对。为了可视化携带乳腺癌的SLN，我们将ErNPs通过balixafortide（ErNPs@POL6326）进行修饰，这是一个化学因子受体CXCR4的肽拮抗剂。当通过皮下途径输送时，ErNPs@POL6326探针能够很容易地引流到SLNs，并通过CXCR4介导的内吞作用特异性地进入转移性乳腺肿瘤细胞。与肿瘤阴性SLN相比，近红外荧光信号在肿瘤阳性SLN中显著增加，能够准确判断SLN乳腺癌转移。在一个同种移植小鼠乳腺肿瘤模型和一个人类乳腺癌异种移植模型中，SLN转移的检测灵敏度分别为92.86%和93.33%，特异度分别为96.15%和96.08%。值得注意的是，这些探针可以准确检测到SLN的巨转移和微转移。总体而言，这些结果突出了ErNPs@POL6326用于SLNs实时可视化和体内SLN转移筛查的潜力。

Sentinel lymph node (SLN) biopsy plays a critical role in axillary staging of breast cancer. However, traditional SLN mapping does not accurately discern the presence or absence of metastatic disease. Detection of SLN metastasis largely hinges on examination of frozen sections or paraffin-embedded tissues post-SLN biopsy. To improve detection of SLN metastasis, we developed a second near-infrared (NIR-II) in vivo fluorescence imaging system, pairing erbium-based rare-earth nanoparticles (ErNPs) with bright down-conversion fluorescence at 1556 nm. To visualize SLNs bearing breast cancer, ErNPs were modified by balixafortide (ErNPs@POL6326), a peptide antagonist of the chemokine receptor CXCR4. The ErNPs@POL6326 probes readily drained into SLNs when delivered subcutaneously, entering metastatic breast tumor cells specifically via CXCR4-mediated endocytosis. NIR fluorescence signals increased significantly in tumor-positive versus tumor-negative SLNs, enabling accurate determination of SLN breast cancer metastasis. In a syngeneic mouse mammary tumor model and a human breast cancer xenograft model, sensitivity for SLN metastasis detection was 92.86% and 93.33%, respectively, and specificity was 96.15% and 96.08%, respectively. Of note, the probes accurately detected both macrometastases and micrometastases in SLNs. These results overall underscore the potential of ErNPs@POL6326 for real-time visualization of SLNs and in vivo screening for SLN metastasis.