Metastatic breast cancer remains a significant source of mortality amongst breast cancer patients and is generally considered incurable in part due to the difficulty in detection of early micro-metastases. The pre-metastatic niche (PMN) is a tissue microenvironment that has undergone changes to support the colonization and growth of circulating tumor cells, a key component of which is the myeloid-derived suppressor cell (MDSC). Therefore, the MDSC has been identified as a potential biomarker for PMN formation, the detection of which would enable clinicians to proactively treat metastases. However, there is currently no technology capable of the in situ detection of MDSCs available in the clinic. Here, we propose the use of shortwave infrared-emitting nanoprobes for the tracking of MDSCs and identification of the PMN. Our rare-earth albumin nanocomposites (ReANCs) are engineered to bind the Gr-1 surface marker of murine MDSCs. When delivered intravenously in murine models of breast cancer with high rates of metastasis, the targeted ReANCs demonstrated an increase in localization to the lungs in comparison to control ReANCs. However, no difference was seen in the model with slower rates of metastasis. This highlights the potential utility of MDSC-targeted nanoprobes to assess PMN development and prognosticate disease progression.

中文翻译：

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通过短波红外纳米探针早期检测肺转移前微环境中的骨髓源性抑制细胞

转移性乳腺癌仍然是乳腺癌患者死亡的重要来源，并且通常被认为是无法治愈的，部分原因是难以检测到早期微转移。转移前生态位 (PMN) 是一种组织微环境，它发生了变化以支持循环肿瘤细胞的定植和生长，其中的关键组成部分是骨髓源性抑制细胞 (MDSC)。因此，MDSC 已被确定为 PMN 形成的潜在生物标志物，其检测将使临床医生能够主动治疗转移。然而，目前临床上尚无能够原位检测MDSC的技术。在这里，我们建议使用短波红外发射纳米探针来跟踪 MDSC 和识别 PMN。我们的稀土白蛋白纳米复合材料 (ReANC) 经过精心设计，可结合小鼠 MDSC 的 Gr-1 表面标记。当在高转移率乳腺癌小鼠模型中静脉注射时，与对照 ReANC 相比，靶向 ReANC 的肺部定位有所增加。然而，在转移率较慢的模型中没有发现差异。这凸显了 MDSC 靶向纳米探针在评估 PMN 发育和预测疾病进展方面的潜在效用。