FGFR特异性核酸适体的筛选及在分子标记和靶向药物载体中的应用

项目名称： FGFR特异性核酸适体的筛选及在分子标记和靶向药物载体中的应用

项目编号： No.81471773

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 王文超

作者单位： 中国科学院合肥物质科学研究院

项目金额： 73万元

中文摘要： 核酸适体 (aptamers) 是从体外随机核酸文库中筛选得到的，能与生物靶标高特异性、高亲和力结合的配体。凭借其核酸组成成分的优异生化特性，适体自从上世纪九十年代开始就被广泛的应用于生物医学的各个领域，与普遍使用的抗体类大分子药物和小分子药物相比，适体越来越体现出其独特的优越性。本课题以在人类恶性肿瘤中普遍发生异常活化的成纤维细胞生长因子受体 (FGFR) 通路为切入点，探索适体在药物治疗和疾病诊断等方向的应用价值。本项目将以FGFR胞外区为靶点，通过在细胞层次上的体外富集筛选，获得高亲和力的FGFR特异性结合的核酸适体，并检测这些适体作为抑癌药物对肿瘤细胞生长的影响。同时，将探索这些适体作为荧光探针在特异性检测FGFR阳性肿瘤细胞的应用，以及作为药物载体在靶向抗癌药物治疗中的应用。

中文关键词： 靶向治疗；纳米颗粒；药物载体；生物医学工程；荧光探针

英文摘要： Aptamers are nucleic acid based molecules with high affinity and specificity against a wide range of biological targets, and are obtained through in vitro selection from random pools of short DNA or RNA fragments. Thanks to the superior biochemical properties of aptamers' nucleic acid components, aptamers have been widely used in every aspect of biomedical research since the 90s of the last century when aptamers were first developed. Compared to the commonly used antibody based protein drugs and small molecule inhibitors, aptamers exhibit many unique advantages. This project will start with one of the most common abnormal signaling pathways in human cancers, the FGFR pathway, to develop specific aptamers that are able to bind to the extracellular domain of FGFR with high affinities through in vitro selection. These aptamers will be tested for their inhibitory effects on tumor cell proliferation. In addition, we will also explore the potential application of these aptamers as fluorescence probes for detecting FGFR positive tumor cells and as drug vectors in targeted drug delivery for cancer.

英文关键词： targeted therapy;nanoparticles;drug vehicle;biomedical engineering;fluorescent probe