Platelet-Leukocyte Hybrid Membrane-Coated Immunomagnetic Beads for Highly Efficient and Highly Specific Isolation of Circulating Tumor Cells
Platelet-Leukocyte Hybrid Membrane-Coated Immunomagnetic Beads for Highly Efficient and Highly Specific Isolation of Circulating Tumor Cells
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血小板-白细胞杂交膜包被的免疫磁珠用于高效、高特异性分离循环肿瘤细胞
DOI：
10.1002/adfm.201803531
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发表时间：
2018-08-22
影响因子：
19
通讯作者：
Liu, Wei
中科院分区：
文献类型：
--
作者：
Rao, Lang;Meng, Qian-Fang;Liu, Wei
具有理想特征的仿生细胞膜伪装纳米颗粒已广泛用于各种生物医学应用。然而，目前的研究主要集中在单细胞膜涂层上，使用多个细胞膜进行纳米颗粒功能化仍然具有挑战性。在这项工作中，血小板（PLT）和白细胞（WBC）膜融合，PLT-WBC混合膜被包被到磁珠上，然后用特异性抗体修饰其表面。由此产生的PLT-WBC混合膜包被免疫磁珠（HM-IMB）继承了PLT增强的癌细胞结合能力，并减少了WBC的同源WBC相互作用，并进一步用于高效和高度特异性地分离循环肿瘤细胞（CTC）。通过使用加标血样，发现与商业IMB相比，HM-IMB的细胞分离效率从66.68%提高到91.77%，细胞纯度从66.53%提高到96.98%。此外，通过使用 HM-IMB，在从乳腺癌患者采集的 20 个临床血液样本中成功鉴定出 19 个高纯度的 CTC。最后，HM-IMB的稳健性在下游CTC分析中得到验证，例如PIK3CA基因突变的检测。预计这种新颖的混合膜涂层策略将为克服当前治疗诊断平台的局限性开辟新的可能性。
Biomimetic cell-membrane-camouflaged nanoparticles with desirable features have been widely used for various biomedical applications. However, the current research focuses on single cell membrane coating and using multiple cell membranes for nanoparticle functionalization is still challenging. In this work, platelet (PLT) and leukocyte (WBC) membranes are fused, PLT-WBC hybrid membranes are coated onto magnetic beads, and then their surface is modified with specific antibodies. The resulting PLT-WBC hybrid membrane-coated immunomagnetic beads (HM-IMBs) inherit enhanced cancer cell binding ability from PLTs and reduce homologous WBC interaction from WBCs, and are further used for highly efficient and highly specific isolation of circulating tumor cells (CTCs). By using spiked blood samples, it is found that, compared with commercial IMBs, the cell separation efficiency of HM-IMBs is improved to 91.77% from 66.68% and the cell purity is improved to 96.98% from 66.53%. Furthermore, by using the HM-IMBs, highly pure CTCs are successfully identified in 19 out of 20 clinical blood samples collected from breast cancer patients. Finally, the robustness of HM-IMBs is verified in downstream CTC analysis such as the detection of PIK3CA gene mutations. It is anticipated that this novel hybrid membrane coating strategy will open new possibilities for overcoming the limitations of current theranostic platforms.