基于适配子的靶向治疗药物研究进展

Advances in the study of aptamer-based drug for targeting therapy

适配子是应用指数富集的配体系统进化技术(systematic evolution of ligands by exponential enrichment,SELEX)从单链随机寡核苷酸文库中筛选得到的,能与靶标高特异性、高亲和力结合的配体,靶点可以是金属离子、核酸、蛋白质、有机物甚至整个有机体。适配子作为靶向治疗及诊断药物有效应用于癌症、黄斑变性、急性冠脉综合征和血管性血友病等疾病,同时也可作为药物的靶向配体,协助药物在特定的组织位点释放。与其他靶向配体相比,适配子因其独特的优势,可针对靶向治疗开发适配子-药物偶联物(aptamer-drug conjugates,Ap DCs),进而促进了生物分析和生物医学的发展。本文总结了近年适配子类靶向治疗药物的研究及临床试验进展,并阐述了其在生物医学中的前景优势和面临的挑战。

Aptamers are randomly selected from single-stranded oligonucleotide libraries by systematic evolution of ligands technology exponential enrichment（SELEX）. They bind to various targets like metal ions, nucleic acids, proteins, small organic compounds, and even entire organisms. Candidate aptamers are predicted to be highly effective in producing targeting effects for certain diseases like cancer, macular degeneration, acute coronary syndrome, von Willebrand factor related disorder disease and so on. Aptamers may also serve as drug-carriers helping drugs to be released in specific regions and tissues. Compared with other types of targeting ligands, aptamers have an array of unique advantageous features, which make them promising to develop aptamer-drug conjugates（Ap DCs） for targeted-oriented therapy. Deep investigation into Ap DCs discovery and development may promote the process of biological and biomedical analysis. In this review, we summarize the advances of drug discovery and drug delivery using aptamers in basic and clinical trials in recent years, and meanwhile analyze its advantages and challenges in biomedical studies.