一种多功能 DNA 纳米蝎,用于高效靶向递送 mRNA 治疗药物。
A multifunctional DNA nano-scorpion for highly efficient targeted delivery of mRNA therapeutics.
机构信息
Department of Laboratory Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, P.R. China.
Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, P.R. China.
出版信息
Sci Rep. 2018 Jul 5;8(1):10196. doi: 10.1038/s41598-018-28542-3.
The highly efficient cancer cell targeted delivery plays an important role in precise targeted therapies. Herein, a multifunctional DNA nano-scorpion nanostructure (termed AptDzy-DNS) functioned with aptamers and DNAzyme is developed for highly efficient targeted delivery of mRNA therapeutics in gene therapy. The designed AptDzy-DNS is self-assembled with specific aptamers as "scorpion stingers" for targeting tumor cell and DNAzymes as "scorpion pincers" for targeted gene therapy by cleaving mRNA into fragments. The as-prepared AptDzy-DNS can effectively distinguish cancer cells from normal cells by specific cross-talking between aptamers on AptDzy-DNS and overexpressed cell-surface receptors. In the process of gene therapy, by reacting with Mg-dependent DNAzyme on AptDzy-DNS, the mRNA oligonucleotide in cancer cell is auto-cleaved into broken strand, failing to be translated into corresponding protein. Following, the downregulation protein can block cancer cell growth and realize highly efficient targeted therapies. The results demonstrate that the multifunctional AptDzy-DNS shows promise for targeted cancer cell discrimination, highly efficient targeted delivery of mRNA therapeutics in gene therapy. Thus, this developed strategy provides impressive improvement on gene targeted therapy and paves the way for application of AptDzy-DNS in human cancer targeted therapies.
高效的癌细胞靶向递送在精准靶向治疗中起着重要作用。在此,开发了一种多功能 DNA 纳米蝎结构(称为 AptDzy-DNS),它与适体和 DNA 酶一起作用,用于基因治疗中 mRNA 治疗剂的高效靶向递送。设计的 AptDzy-DNS 是通过将 mRNA 切割成片段,利用特异性适体作为“蝎刺”靶向肿瘤细胞,利用 DNA 酶作为“蝎钳”进行靶向基因治疗而自组装的。所制备的 AptDzy-DNS 可以通过 AptDzy-DNS 上的适体与过表达的细胞表面受体之间的特异性交互作用,有效地将癌细胞与正常细胞区分开来。在基因治疗过程中,通过与 AptDzy-DNS 上的 Mg 依赖性 DNA 酶反应,癌细胞中的 mRNA 寡核苷酸自动切割成断裂链,无法翻译为相应的蛋白质。随后,下调蛋白可以阻断癌细胞生长,实现高效靶向治疗。结果表明,多功能 AptDzy-DNS 显示出用于靶向癌细胞识别和基因治疗中高效靶向递送 mRNA 治疗剂的潜力。因此,该开发策略为基因靶向治疗提供了显著的改进,并为 AptDzy-DNS 在人类癌症靶向治疗中的应用铺平了道路。