Siebert Jake N, Shah Jay V, Tan Mei Chee, Riman Richard E, Pierce Mark C, Lattime Edmund C, Ganapathy Vidya, Moghe Prabhas V
Department of Biomedical Engineering, Rutgers University, 599 Taylor Rd., Piscataway, NJ 08854, USA.
Engineering Product Development, Singapore University of Technology and Design, 8 Somapah Rd., Singapore 487372, Singapore.
Pharmaceutics. 2024 Apr 17;16(4):549. doi: 10.3390/pharmaceutics16040549.
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.
转移性乳腺癌仍然是乳腺癌患者死亡的一个重要原因,部分原因是早期微转移灶难以检测,所以通常被认为无法治愈。前转移微环境(PMN)是一种组织微环境,它已经发生了变化以支持循环肿瘤细胞的定植和生长,其中的一个关键成分是髓源性抑制细胞(MDSC)。因此,MDSC已被确定为PMN形成的潜在生物标志物,检测到它将使临床医生能够积极治疗转移灶。然而,目前临床上还没有能够原位检测MDSC的技术。在此,我们提出使用发射短波红外的纳米探针来追踪MDSC并识别PMN。我们的稀土白蛋白纳米复合材料(ReANCs)经过工程设计,可与小鼠MDSC的Gr-1表面标志物结合。当将其静脉注射到具有高转移率的乳腺癌小鼠模型中时,与对照ReANCs相比,靶向ReANCs在肺部的定位增加。然而,在转移率较低的模型中未观察到差异。这突出了靶向MDSC的纳米探针对评估PMN发育和预测疾病进展的潜在效用。