Surface engineering for efficient capture of circulating tumor cells in renal cell carcinoma: From nanoscale analysis to clinical application
Surface engineering for efficient capture of circulating tumor cells in renal cell carcinoma: From nanoscale analysis to clinical application
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DOI：
10.1016/j.bios.2020.112250
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发表时间：
2020-08-15
影响因子：
12.6
通讯作者：
Hong, Seungpyo
中科院分区：
文献类型：
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作者：
Bu, Jiyoon;Nair, Ashita;Hong, Seungpyo
对来自患者外周血的循环肿瘤细胞（CTC）的灵敏检测有助于按需监测肿瘤进展。然而，肾细胞癌CTC（RCCCTC）的临床显著捕获由于其异质性表面受体表达而仍然难以捉摸。本文中，开发了一种新的捕获平台，通过整合树枝状聚合物介导的多价结合、抗体混合物和仿生细胞滚动来检测RCC-CTC。使用原子力显微镜测量的纳米级结合动力学揭示，树枝状聚合物涂覆的表面表现出一个数量级的增强解离速率动力学相比，表面没有树枝状聚合物，这转化为细胞捕获改善了类似的60%。选择素诱导的细胞滚动促进癌细胞的表面募集，进一步提高癌细胞捕获高达1.7倍。最后，靶向四种RCC-CTC表面受体（包括上皮细胞粘附分子（EpCAM）、碳酸酐酶IX（CA 9）、表皮生长因子受体（EGFR）和肝细胞生长因子受体（c-Met））的抗体混合物将RCC细胞的捕获提高高达80%。最佳表面配置优于仅依赖EpCAM的传统检测，正如在患者样本中检测到显着更多的CTCs所证明的那样（9.8 +/- 5.1 vs. 1.8 +/- 2.0 CTCs mL（-1））。这些结果表明，新工程化的捕获平台有效地检测RCC-CTC作为肿瘤生物标志物的潜在用途。
Sensitive detection of circulating tumor cells (CTCs) from patients' peripheral blood facilitates on-demand monitoring of tumor progression. However, clinically significant capture of renal cell carcinoma CTCs (RCCCTCs) remains elusive due to their heterogenous surface receptor expression. Herein, a novel capture platform is developed to detect RCC-CTCs through integration of dendrimer-mediated multivalent binding, a mixture of antibodies, and biomimetic cell rolling. The nanoscale binding kinetics measured using atomic force microscopy reveal that dendrimer-coated surfaces exhibit an order of magnitude enhancement in off-rate kinetics compared to surface without dendrimers, which translated into cell capture improvements by similar to 60%. Selectin-induced cell rolling facilitates surface recruitment of cancer cells, further improving cancer cell capture by up to 1.7-fold. Lastly, an antibody cocktail targeting four RCC-CTC surface receptors, which included epithelial cell adhesion molecule (EpCAM), carbonic anhydrase IX (CA9), epidermal growth factor receptor (EGFR), and hepatocyte growth factor receptor (c-Met), improves the capture of RCC cells by up to 80%. The optimal surface configuration outperforms the conventional assay solely relying on EpCAM, as demonstrated by detecting significantly more CTCs in patients' samples (9.8 +/- 5.1 vs. 1.8 +/- 2.0 CTCs mL(-1)). These results demonstrate that the newly engineered capture platform effectively detects RCC-CTCs for their potential use as tumor biomarkers.