Behavior of Endogenous Tumor-Associated Macrophages Assessed In Vivo Using a Functionalized Nanoparticle
Behavior of Endogenous Tumor-Associated Macrophages Assessed In Vivo Using a Functionalized Nanoparticle
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DOI：
10.1593/neo.09356
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发表时间：
2009-05-01
期刊：
影响因子：
4.8
通讯作者：
Pittet, Mikael J.
中科院分区：
文献类型：
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作者：
Leimgruber, Antoine;Berger, Cedric;Pittet, Mikael J.
肿瘤相关巨噬细胞(TAM)在许多癌症中侵袭肿瘤间质，但其作用尚不完全清楚。为了可视化和更好地了解这些肿瘤进展中的关键细胞，我们筛选了一组合理选择的可注射药物组合，以在三种不同的癌症模型(结肠癌、肺腺癌和软组织肉瘤)中无处不在地成像内源性TAM。AMTA680是一种功能衍生化的磁性荧光纳米颗粒，它标记了一组具有“M2”巨噬细胞表型的髓系细胞，而其他邻近细胞，包括肿瘤细胞和各种其他白细胞，仍未标记。我们进一步表明，AMTA680标记的内源性TAMs没有改变，可以在不同的分辨率下使用各种成像方式进行非侵入性追踪，例如荧光分子断层成像、磁共振成像、多光子和共聚焦活体显微镜。对体内分布和活性的定量评估表明，这些细胞聚集在肿瘤内划定的病灶中，表现出相对较低的运动性，并延长了细胞质突起，以延长与邻近肿瘤细胞的物理相互作用。非侵入性成像也可用于定量监测耗竭方案。因此，AMTA680或相关的细胞靶向剂是体内分析肿瘤微环境的合适的注射载体。
Tumor-associated macrophages (TAMs) invade the tumor stroma in many cancers, yet their role is incompletely understood. To visualize and better understand these critical cells in tumor progression, we screened a portfolio of rationally selected, injectable agents to image endogenous TAMs ubiquitously in three different cancer models (colon carcinoma, lung adenocarcinoma, and soft tissue sarcoma). AMTA680, a functionally derivatized magneto-fluorescent nanoparticle, labeled a subset of myeloid cells with an "M2" macrophage phenotype, whereas other neighboring cells, including tumor cells and a variety of other leukocytes, remained unlabeled. We further show that AMTA680-labeled endogenous TAMs are not altered and can be tracked noninvasively at different resolutions and using various imaging modalities, e. g., fluorescence molecular tomography, magnetic resonance imaging, and multiphoton and confocal intravital microscopy. Quantitative assessment of TAM distribution and activity in vivo identified that these cells cluster in delimited foci within tumors, show relatively low motility, and extend cytoplasmic protrusions for prolonged physical interactions with neighboring tumor cells. Noninvasive imaging can also be used to monitor TAM-depleting regimen quantitatively. Thus, AMTA680 or related cell-targeting agents represent appropriate injectable vehicles for in vivo analysis of the tumor microenvironment.