Etayash Hashem, Jiang Keren, Azmi Sarfuddin, Thundat Thomas, Kaur Kamaljit
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, T6G 2E1, Canada.
Department of Chemical and Materials Engineering, University of Alberta, Edmonton, Alberta, T6G 2V4, Canada.
Sci Rep. 2015 Oct 5;5:13967. doi: 10.1038/srep13967.
Ligand-directed targeting and capturing of cancer cells is a new approach for detecting circulating tumor cells (CTCs). Ligands such as antibodies have been successfully used for capturing cancer cells and an antibody based system (CellSearch(®)) is currently used clinically to enumerate CTCs. Here we report the use of a peptide moiety in conjunction with a microcantilever array system to selectively detect CTCs resulting from cancer, specifically breast cancer. A sensing microcantilever, functionalized with a breast cancer specific peptide 18-4 (WxEAAYQrFL), showed significant deflection on cancer cell (MCF7 and MDA-MB-231) binding compared to when exposed to noncancerous (MCF10A and HUVEC) cells. The peptide-functionalized microcantilever allowed efficient capture and detection of cancer cells in MCF7 spiked human blood samples emulating CTCs in human blood. A detection limit of 50-100 cancer cells mL(-1) from blood samples was achieved with a capture yield of 80% from spiked whole blood samples. The results emphasize the potential of peptide 18-4 as a novel peptide for capturing and detecting cancer cells in conjunction with nanomechanical cantilever platform. The reported peptide-based cantilever platform represents a new analytical approach that can lead to an alternative to the various detection platforms and can be leveraged to further study CTCs.
配体导向的癌细胞靶向与捕获是检测循环肿瘤细胞(CTC)的一种新方法。诸如抗体之类的配体已成功用于捕获癌细胞,一种基于抗体的系统(CellSearch(®))目前在临床上用于计数CTC。在此,我们报告了将肽部分与微悬臂梁阵列系统结合使用,以选择性地检测癌症(特别是乳腺癌)产生的CTC。用乳腺癌特异性肽18 - 4(WxEAAYQrFL)功能化的传感微悬臂梁,与暴露于非癌细胞(MCF10A和HUVEC)时相比,在与癌细胞(MCF7和MDA - MB - 231)结合时显示出明显的偏转。肽功能化的微悬臂梁能够在模拟人血液中CTC的MCF7加标人血样本中高效捕获和检测癌细胞。从血样中实现了50 - 100个癌细胞mL(-1)的检测限,从加标的全血样本中捕获率为80%。结果强调了肽18 - 4作为一种新型肽与纳米机械悬臂梁平台结合用于捕获和检测癌细胞的潜力。所报道的基于肽的悬臂梁平台代表了一种新的分析方法,它可以成为各种检测平台的替代方法,并可用于进一步研究CTC。