Layer-by-layer fabrication of alginate/polyethyleneimine multilayer on magnetic interface with enhanced efficiency in immuno-capturing circulating tumor cells

磁性界面上海藻酸盐/聚乙烯亚胺多层的逐层制备及其在免疫捕获循环肿瘤细胞方面的增强效率

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作者:Yang Xiao, Zhiyi Zhou, Yifan Zuo, Xueyuan Wu, Yuping Liu, Yichen Li, Yuetong Gao, Xiashu Zhang, Yu Wang, Lili Hu, Chenglin Li

Background

The technology of capturing circulating tumor cells (CTCs) plays a crucial role in the diagnosis, evaluation of therapeutic efficacy, and prediction of prognosis in lung cancer. However, the presence of complex blood environment often

Results

We present a novel immune magnetic probe Fe3O4@(PEI/AA)4@Apt. The surface of Fe3O4 particles was modified with four layers of PEI/AA composite by layer-by-layer assembly. Furthermore, aptamers targeting epithelial marker EpCAM (SYL3C) and mesenchymal marker CSV (ZY5C) were simultaneously connected on Fe3O4@(PEI/AA)4 to improve the detection of different phenotypic CTCs and reduce false negatives. The results demonstrated that the (PEI/AA)4 coatings not only minimized non-specific protein adsorptions, but also significantly reduced the adsorption rate of red blood cells to a mere 1 %, as a result of which, the Fe3O4@(PEI/AA)4@Apt probe achieved a remarkably high capture efficiency toward CTCs (95.9 %). In the subsequent validation of clinical samples, the probe was also effective in capturing rare CTCs from lung cancer patients. Significance and novelty: A (PEI/AA) polymerized composite with controllable layers was fabricated by layer-by-layer self-assembly technique, which displayed remarkable anti-nonspecific adsorption capabilities toward proteins and cells. Importantly, Fe3O4@(PEI/AA)4@Apt probe significantly improved CTCs capture purity in lung cancer patients to 89.36 %. For the first time, this study combined controllable (PEI/AA) layers with magnetic separation to innovatively build a resistant interface that significantly improves the specific capture performances of CTCs, broadening the application of this polymerized composite.

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