Mitchell Michael J, Castellanos Carlos A, King Michael R
Department of Biomedical Engineering, Cornell University, Ithaca, NY 14853, USA; David H. Koch Institute for Integrative Cancer Research, Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Department of Biomedical Engineering, Cornell University, Ithaca, NY 14853, USA.
Biomaterials. 2015 Jul;56:179-86. doi: 10.1016/j.biomaterials.2015.03.045. Epub 2015 Apr 17.
The metastatic spread of cancer cells from the primary tumor to distant sites leads to a poor prognosis in cancers originating from multiple organs. Increasing evidence has linked selectin-based adhesion between circulating tumor cells (CTCs) and endothelial cells of the microvasculature to metastatic dissemination, in a manner similar to leukocyte adhesion during inflammation. Functionalized biomaterial surfaces hold promise as a diagnostic tool to separate CTCs and potentially treat metastasis, utilizing antibody and selectin-mediated interactions for cell capture under flow. However, capture at high purity levels is challenged by the fact that CTCs and leukocytes both possess selectin ligands. Here, a straightforward technique to functionalize and alter the charge of naturally occurring halloysite nanotubes using surfactants is reported to induce robust, differential adhesion of tumor cells and blood cells to nanotube-coated surfaces under flow. Negatively charged sodium dodecanoate-functionalized nanotubes simultaneously enhanced tumor cell capture while negating leukocyte adhesion, both in the presence and absence of adhesion proteins, and can be utilized to isolate circulating tumor cells regardless of biomarker expression. Conversely, diminishing nanotube charge via functionalization with decyltrimethylammonium bromide both abolished tumor cell capture while promoting leukocyte adhesion.
癌细胞从原发性肿瘤转移至远处会导致源自多个器官的癌症预后不良。越来越多的证据表明,循环肿瘤细胞(CTC)与微脉管系统内皮细胞之间基于选择素的黏附与转移扩散有关,其方式类似于炎症期间白细胞的黏附。功能化生物材料表面有望成为一种诊断工具,用于分离CTC并有可能治疗转移,利用抗体和选择素介导的相互作用在流动条件下捕获细胞。然而,由于CTC和白细胞都具有选择素配体,实现高纯度捕获面临挑战。在此,报道了一种使用表面活性剂对天然埃洛石纳米管进行功能化和改变电荷的简单技术,以在流动条件下诱导肿瘤细胞和血细胞对纳米管涂层表面产生强大的差异黏附。带负电荷的十二烷基酸钠功能化纳米管在有和没有黏附蛋白的情况下,都能同时增强肿瘤细胞捕获并抑制白细胞黏附,并且可用于分离循环肿瘤细胞,而不考虑生物标志物的表达。相反,通过用溴化十二烷基三甲基铵功能化来减少纳米管电荷,既消除了肿瘤细胞捕获,又促进了白细胞黏附。