Photoluminescent carbon nanotubes interrogate the permeability of multicellular tumor spheroids.
Photoluminescent carbon nanotubes interrogate the permeability of multicellular tumor spheroids.
复制标题
DOI：
10.1016/j.carbon.2015.08.024
复制
发表时间：
2016-02-01
期刊：
影响因子：
10.9
通讯作者：
Heller DA
中科院分区：
文献类型：
--
作者：
Jena PV;Shamay Y;Shah J;Roxbury D;Paknejad N;Heller DA
纳米材料在抗癌药物输送和成像应用方面得到了广泛的研究。在二维细胞培养系统中显示出希望的纳米颗粒在更复杂的环境中往往失败，可能是因为缺乏对密集的三维结构的穿透。多细胞肿瘤球体是一种在体外细胞培养环境中研究纳米粒子与3D相互作用的新兴模型系统。利用半导体碳纳米管的本征近红外发射，在三维体积内光学重建其局域，求解了两个不同的多细胞肿瘤球体的相对渗透率。纳米管的光致发光显示，纳米管迅速内化到MCF-7乳腺癌细胞衍生的球体中，而它们几乎没有穿透到我们从小鼠肝癌细胞系SK-136衍生的球体中。通过电子显微镜和免疫组织化学对球体的表征表明，细胞外基质和间质间距存在很大差异，这与纳米管的穿透直接相关。这个平台预示着一种新的方法来表征活的多细胞环境的渗透性。
Nanomaterials have been extensively investigated for cancer drug delivery and imaging applications. Nanoparticles that show promise in two-dimensional cell culture systems often fail in more complex environments, possibly due to the lack of penetration in dense, three-dimensional structures. Multicellular tumor spheroids are an emerging model system to investigate interactions of nanoparticles with 3D in vitro cell culture environments. Using the intrinsic near-infrared emission of semiconducting carbon nanotubes to optically reconstruct their localization within a three-dimensional volume, we resolved the relative permeability of two different multicellular tumor spheroids. Nanotube photoluminescence revealed that nanotubes rapidly internalized into MCF-7 breast cancer cell-derived spheroids, whereas they exhibited little penetration into spheroids derived from SK-136, a cell line that we developed from murine liver cancer. Characterization of the spheroids by electron microscopy and immunohistochemistry revealed large differences in the extracellular matrix and interstitial spacing, which correlated directly with nanotube penetration. This platform portends a new approach to characterize the permeability of living multicellular environments.