Self-assembled RNA-triple helix hydrogel drug delivery system targeting triple-negative breast cancer
The main problems involved traditional RNA cancer therapies include low cellular uptake in vitro or in vivo, instability of in vivo circulation, nonspecific bio-distribution, and lack of targeting ability, which result poor silencing efficiency. Herein, we developed a novel RNA-triple-helix hydrogel for treatment of triple negative breast cancers (TNBCs) by incorporating RNA-triple-helix and siRNA duplexes of CXCR4 into the same RNA nanoparticles with no synthetic polycationic reagents added. The RNA-triple-helix consists of one tumour suppressor miRNA (miRNA-205) and one oncomiR inhibitor (miRNA-221), both of which showed outstanding effect in synergistically abrogating tumours. The siRNA duplexes of CXCR4 were embedded into the RNA hydrogel to block breast cancer metastasis and conjugation of LXL-DNA aptamer (apt-DNA-Chol) is an effective target DNA sequence for MDA-MB-231 cell. The self-assembly of RNA-triple-helix hydrogel exhibited high selectivity of in vitro and in vivo absorption and controlling miRNA expression when compared to free miRNA and RNA transcripts. The well-developed gene delivery system provided a potential treatment with high specificity and selectivity toward TNBCs. This strategy can be implemented in triplex-helix hydrogel design to form novel miRNA combinations to treat various human cancers.
- This article is part of the themed collection: 2019 Journal of Materials Chemistry B HOT Papers