DNA Nanosponge for Adsorption and Clearance of Intracellular miR-21 and Enhanced Antitumor Chemotherapy

【作者】Kaixiang Zhang, Junjie Liu, Qiaoli Song, Xue Yang, Danyu Wang, Wei Liu, Jinjin Shi, Zhenzhong Zhang

【期刊名】ACS Appl. Mater. Interfaces

【影响因子】 2019年:8.456

【作者单位】School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, PR China

【年，卷(期)：页码】2019, 11(50): 46604–46613

【关键词】DNA nanosponge, miRNA-21, antisense oligonucleotide, cell apoptosis, enhanced chemotherapy

【摘要】Antisense oligonucleotide (ASO)-induced cellular signaling pathway alteration is evolving as a promising therapeutic strategy for improving antitumor chemotherapy. However, the inherent instability and inefficiency of ASO delivery remain major hurdles for its application. Herein, we developed a self-assembled DNA nanosponge (DNS) for adsorption and clearance of intracellular miR-21. The densely packed DNA nanostructure is able to provide large amounts of repeated ASO copies for efficient capturing of miR-21 and inhibiting the miRNAs function in mammalian cells. The cell apoptosis-related protein expression (Bcl-2, Bax, and cleaved caspase-3/9) can be obviously interrupted with the delivery of DNS. Besides, we have shown that the DNS can efficiently carry Dox for chemotherapy and inducing tumor cell (MCF-7) apoptosis meanwhile has little affect to normal cells (Hs578 Bst). These polymeric DNS systems mimic the natural RNA circle-based miRNA sponges and have potential to be applied for specific and efficient regulation of gene expression in tumor cells for synergistic antitumor chemotherapy.

【全文链接】https://www.sciencedirect.com/science/article/pii/S0168365919307485