针对细胞识别的人工抗体材料制备及其在循环肿瘤细胞捕获中的应用

针对目前循环肿瘤细胞富集过程中特异性抗体缺乏、抗体使用和保存条件苛刻、重复使用困难的问题。本项目以肿瘤细胞作为分子印迹的模板分子，通过细胞印迹聚合物体系的研究，并且辅以亲和配基的特异性相互作用，制备基于多识别机理的人工抗体材料，建立人工抗体材料富集肿瘤细胞的检测方法，并通过构建人工抗体吸附细胞的动力学和热力学模型，揭示其识别细胞的机理。通过该材料在肝癌肿瘤患者血液中的应用研究，实现CTCs的特异性捕获。此外，基于聚合物接枝反应以及可逆加成-断裂链转移聚合，制备两亲性刷状聚合物和活性/可控聚合物链段，作为人工抗体材料的共混改性聚合物，从而降低人工抗体材料的抗污染性能，提高对目标细胞的选择性。该研究成果不仅可以实现血液中CTCs的特异性捕获，而且有望为针对其他生物模板（如细菌、病毒等）识别的人工抗体材料的研制提供理论指导和相关技术。

The enrichment of circulating tumor cells (CTCs) is challenged by the shortage of the specific antibody, and the delicate conditions on the antibody storage and application. In this project, the tumor cell will be selected as the template for the fabrication of the molecularly imprinted materials. According to the study on the fabrication of molecularly imprinted materials and affinity ligands-based interaction, multiple recognition mechanism-based artificial antibody will be prepared, then the measurement will be built towards the CTCs detection. The mechanism on the recognition of the artificial antibodies towards the cell will be studied by the cell adsorption thermodynamics and kinetics on the materials. The application study on blood from the liver cancer patients will be conducted to achieve the the specific capture towards CTCs in the real sample. In addition, amphipathy brush polymer and controlled/living polymer chain will be prepared by the polymer grafting reaction and reversible addition-fragmentation chain transfer (RAFT) polymerization. Then, they will be applied as the blended polymers to improve the anti-fouling properties of the artificial antibody, which would further improve the selectivity of the recognition sites. This project would not only provide an effective way to capture CTCs in the blood, but also offer the universal theoretical guidance and related techniques towards other microorganism imprinting, such as bacteria and virus.