Anti-miR21-conjugated DNA nanohydrogel for enhanced cancer therapy

MicroRNAs (miRNAs) are non-coding, endogenous small single-stranded RNA molecules involved in post-transcriptional regulation of gene expression. It has been demonstrated that dysregulation of miRNA plays a major role in tumor formation, proliferation, and metastasis. Therefore, the delivery of anti-miRNA oligonucleotides to block the activity of these oncogenic miRNAs is a high-potential anti-cancer therapy approach. In particular, miRNA-21 (miR-21) can be an excellent target as it is an oncogenic miRNA that is upregulated in various cancers including glioblastoma, breast cancer, and colon cancer. However, anti-miRNAs are unstable in the physiological environment and have low cell membrane permeability, making it difficult to accumulate at certain concentrations to have anti-cancer effects within cancer cells. To overcome these difficulties, we developed anti-miR-21 functionalized DNA hydrogel (amiR-21 Dgel). We confirmed the improved physiological stability of amiR-21 Dgel in vitro, and observed that it blocked up to 96.6 % of miR-21 in HeLa cells, and reduced cell viability down to 77.9 % for 72 h. In particular, RT-qPCR analysis demonstrated that blocking of miR-21 induces increased mRNA expression of the tumor suppressor genes, PTEN and PDCD4 by 6.23- and 6.87-fold, respectively. In addition, the Dgel can act as a drug delivery vehicle, intercalating anticancer drugs such as doxorubicin (Dox) to be delivered into cells. DOX, an anticancer drug, showed a synergistic anticancer effect with amiR-21, which was delivered together. We expect that this approach will be a convenient to optimization and highly effective strategy for anticancer therapy employing antisense miRNAs.