磁性埃洛石纳米管聚合体系的组装及对外循环肿瘤细胞的吸附与分离研究

针对癌症病人血样中外循环肿瘤细胞分离富集所面临的捕获效率低、特异性不高以及抗体寿命短、易失活，高成本等问题，本项目采用表面印迹及磁分离技术，设计并合成一种对外循环肿瘤细胞表面特异性抗原蛋白—EGFR突变体具有独特识别性能的新型磁性埃洛石核-壳结构蛋白质印迹聚合物，并将合成的聚合物吸附在外循环肿瘤细胞表面，外加磁场下实现癌症病人血液样品中外循环肿瘤细胞的高效分离与富集；从蛋白质结构-主客体位点间作用力-印迹蛋白吸附行为入手，设计一类理想的蛋白质印迹自组装体系，提出并验证水相体系中表面印迹技术分离富集蛋白质的“双亲性多位点匹配机理”，解决以往蛋白质印迹过程中单体选择的盲目性，为高效率筛选蛋白质印迹体系提供重要的参考价值。项目的成功，将表面分子印迹技术应用到外循环肿瘤细胞的吸附与分离，在肿瘤的分期诊断、治疗方案的快速评估、肿瘤复发的监测以及肿瘤新药物的开发等方面具有重大的实际应用价值。

Nowadays the detection of circulating tumor cells from blood samples of cancer patients is facing many problems including low specificity, low capture efficiency and serious destruction to the target protein. Therefore, a new type of magnetic halloysite core-shell structure imprinted polymer spheres for specifically recognizing protein-EGFR mutant from circulating tumor cells was designed and synthesized utilizing surface imprinting technology and magnetic separation technology. The obtained polymer was adsorbed onto the surface of circulating tumor cells to achieve efficient separation and enrichment of circulating tumor cells from blood samples of cancer patients under external magnetic field. Based on the molecular design, the host-guest intermolecular interaction, and adsorption and desorption of imprinting molecule, a new type of imprinting self-assembly system was designed and “multiple points amphiphilic matching mechanism” of surface imprinting technology for separation and enrichment of proteins in the aquatic phase system was proposed and verified, which would solve the randomness of monomer choice in the process of protein imprinting and provide considerable value for efficient screening of protein imprinting system. The surface molecular imprinting technique will be successfully applied to the adsorption and separation of circulating tumor，which possess great theoretical and practical values for tumor staging diagnosis, rapid assessment of treatment programs, monitoring of tumor recurrence and development of anti-tumor drug.