磁性纳米印迹MOF复合材料的构建及其对ctDNA的多重特异性富集

Circulating tumor DNA (ctDNA) as a new molecular tumor marker has been used for early diagnosis and dynamic monitor of tumor, as well as individualized treatment guidance due to high specificity, less intratumoral heterogeneity influence, and less invasion. Whereas the amount of ctDNA in the cancer patients’ plasma is so low that could be analyzed. In this program, magnetic nano-imprinted MOF composite materials are constructed via a multi-specific recognition strategy based on appropriate MOF material platform for high specific ctDNA enrichment. Amino group functionalized magnetic nano-imprinted MOF composite materials are synthesized under room temperature using methylimidazole and aminoimidazole as double organic ligand and Zn2+ as metal ion source, and similar DNA as nano-imprinted molecular via coordination chemistry, molecular imprinted technology and metal-ligand-fragment coassembly. PEG is introduced in this system to reduce nonspecific protein adsorption. This project not only obtain high purity target ctDNA via high selective and low cost magnetic enrichment but also develop a new ctDNA enrichment technology.

循环肿瘤DNA（ctDNA），一种新型分子肿瘤标志物，因其特异性高、受肿瘤异质性影响小，微创等优势，可用于肿瘤早期诊断。因此，对ctDNA的研究具有极其重要的生物学意义和临床应用价值。然而在癌症病人血浆中ctDNA含量极低，为后续分析带来巨大挑战。本项目拟通过选择合适的MOFs为材料平台，利用多重特异性识别策略，构筑磁性纳米印迹MOF复合材料，用于高效富集ctDNA。通过配位化学原理、分子印迹技术及金属-配体-碎片共组装技术，以甲基咪唑和氨基咪唑为双有机配体，Zn2+等为金属源，与目标ctDNA尺寸接近DNA为纳米印迹分子，在磁性纳米球表面可控包覆，室温一步制备氨基功能化磁性纳米印迹MOF复合材料。引入具有抗蛋白非特异性吸附的PEG，阻止环境中蛋白质等非特异性吸附。利用材料优异的磁性能，分离获得高纯度目标ctDNA，实现对ctDNA的高选择性、低成本富集。

癌症是一类严重危害人类健康的重大疾病，致死率较高。对癌症的早期诊断和治疗是降低致死率的主要途径。利用ctDNA早期诊断肿瘤，灵敏度高、准确度高、假阳性率低。然而ctDNA含量低，为后续分析带来巨大挑战。本项目以ctDNA为目标物，设计合成了具有特异性识别、高效富集、检测的多功能磁性纳米复合材料，为发展新型的ctDNA检测技术提供理论依据和技术支撑。这些材料展现了对ctDNA的高选择性和低检测限。在对癌症病人诊断研究中，这些材料能够高特异性地识别、富集、检测ctDNA，表现出较大的临床应用前景。