Taoye Zhang,Wei Peng,Wanli Jiang,Kefan Gao,Wei Liu
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.
Rare circulating tumor cells (CTCs) are always harvested with large numbers of white blood cells (WBCs) by current CTC isolation techniques, which influences the accuracy of CTC-related gene and protein analysis. Therefore, it is very urgent to develop a method for efficient isolation of CTCs with high purity. In this work, we fabricated a reversibly assembled interface by layer-by-layer assembly of biotinylated poly-(L-lysine-graft-ethylene glycol) (PLL-g-PEG-biotin), streptavidin, and CTC-specific antibody on a three-dimensional conductive scaffold, and further embedded it into a customized microchip for CTC capture. The assembled multilayers increased the roughness of the scaffold, which improved the capture efficiency. Importantly, the PLL-g-PEG-biotin covalently coupled with CTCs could be detached from the scaffold by electrostatic repulsion, and the released CTCs could be recaptured on the conductive scaffold via electrostatic attraction while the WBCs were continuously drifted away. This reversible capture and release strategy significantly improved the purity of CTCs, and pure CTCs were obtained from cancer patients’ blood samples for gene mutation assay, which will be of great significance for assisting cancer diagnosis and treatment in a noninvasive way.
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