基于感光高分子细胞膜色谱及一珠一肽法多肽库筛选肿瘤靶向肽的研究

肿瘤靶向肽对于癌症的精准治疗日益重要，目前已知肿瘤靶向肽偏少，亟需要开发精准高效筛选肿瘤靶向肽的色谱方法，这对肿瘤细胞膜色谱固定相的制备提出了新的挑战，在制备过程中，如何能够克服传统硅烷化改性试剂的缺点，构筑具有复杂结构、高键合密度、高负载率、高质量、高性能的细胞膜涂层成为一个倍受关注的问题。本课题旨在探讨如何利用水溶性感光高分子的自组装取代毒性大、污染强、易水解的硅烷化试剂，通过对色谱填料表面肿瘤细胞膜涂层制备、性能及一珠一肽法多肽库联用技术的创新，建立具有稳定可控、适合肿瘤靶向肽精准筛选等应用需要的细胞膜色谱固定相自组装构筑的系统方法，以及利用一珠一肽法多肽库和细胞膜色谱技术联用来高效筛选肿瘤靶向肽的系统方法；利用感光高分子独特的光、热诱导原位交联反应实现对自组装细胞膜色谱涂层的共价键合和固定化；研究所制备肿瘤细胞膜色谱固定相的物理化学性质，探索其在肿瘤靶向肽精准高效筛选等方面的应用。

The tumor targeting peptides for accurate cancer treatment is becoming more and more important. Less known tumor targeting peptide, need to develop more accurate and efficient screening method, and propose the new challenge to the preparation of the tumor cell membrane chromatography stationary phase. In the preparation process, how can we overcome the shortcoming of traditional silanizing reagents, building cell membrane coatings with complex structure, high bonding density, high load, high quality and high performance become a problem of wide concern. In our project, the goal is to establish a systematic method to realize the high performance cell membrane stationary phases by controllable layer-by-layer self-assembly technique, and to achieve high efficiency screening of tumor targeting peptides combined with one bead one compound peptide library technique. Instead of the traditional silanizing agents, water soluble photosensitive polymers will be designed and applied to the self-assembly to achieve non-covalent bonded cell membrane coatings on the surfaces of HPLC packing materials, which change to covalent bonded coatings after photocrosslinking. The properties of the obtained tumor cell membrane stationary phases, as well as their applications in the screening of tumor targeting peptides from one bead one compound peptide library will be investigated.