Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan, Hubei 430072, China.
Wuhan University Shenzhen Institution, Shenzhen 518057, China.
ACS Appl Mater Interfaces. 2021 Jun 2;13(21):24543-24552. doi: 10.1021/acsami.1c05806. Epub 2021 May 20.
The isolation and detection of rare circulating tumor cells (CTCs) from patient peripheral blood can help early diagnosis of cancer and evaluation of therapeutic outcomes. At present, most of the available strategies for enriching CTCs face serious problems with purity due to the nonspecific interactions between the capture medium and leukocytes. Inspired by the immune evasion ability of homologous red blood cells (RBCs), we modified the tumor-targeting molecule folic acid (FA) on the surface of RBCs by hydrophobic interactions. Under the treatment of polybrene, the charges on the surface of RBCs are neutralized, which reduces the mutual repulsion force. Furthermore, RBCs treated with polyethylene also have excellent deformability, thereby enabling engineered RBCs to form a dense bionic layer on the adhesive glass slide, which can greatly inhibit the nonspecific adhesion of leukocytes. The bionic layer can achieve high-purity enrichment of tumor cells in phosphate-buffered saline (PBS), and we can achieve high-activity release in plasma. The cell count showed over 80% capture efficiency and over 70% release rate, and the purity of CTCs obtained in the artificial blood sample after release was higher than 90%. The RBC bionic surface coating is notably cost-effective and highly applicable for CTC isolation in clinic practice, and thus provides new prospects for designing cell-material interfaces for advanced cell-based biomedical studies in the future.
从患者外周血中分离和检测稀有循环肿瘤细胞(CTC)有助于癌症的早期诊断和治疗效果评估。目前,大多数富集 CTC 的可用策略由于捕获介质与白细胞之间的非特异性相互作用,其纯度存在严重问题。受同源红细胞(RBC)免疫逃避能力的启发,我们通过疏水相互作用修饰了 RBC 表面的肿瘤靶向分子叶酸(FA)。在聚凝胺的作用下,RBC 表面的电荷被中和,从而减少了相互排斥力。此外,经过聚乙烯处理的 RBC 也具有出色的变形能力,从而使工程化 RBC 能够在粘性玻璃载玻片上形成致密的仿生层,从而可以大大抑制白细胞的非特异性黏附。仿生层可以在磷酸盐缓冲盐水(PBS)中实现对肿瘤细胞的高纯度富集,并且我们可以在血浆中实现高活性释放。细胞计数显示,捕获效率超过 80%,释放率超过 70%,并且在释放后人工血液样本中获得的 CTC 的纯度高于 90%。RBC 仿生表面涂层具有显著的成本效益,非常适用于临床实践中的 CTC 分离,为未来先进的基于细胞的生物医学研究中的细胞-材料界面设计提供了新的前景。