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 was developed, without the synthetic polycationic reagents.

Here, we report a novel magnetic resonance imaging (MRI)/fluorescence bimodal amplification platform for the detection of glutathione (GSH) on the basis of redoxable manganese dioxide (MnO2) nanosheets, which can be readily applied as a DNA nanocarrier, fluorescence quencher, and intracellular GSH-activated MRI contrast agent. The binding of aptamers that absorbed on the MnO2 nanosheets to their target can facilitating the endocytosis of target-nanoprobes. Once endocytosed, the MnO2 nanosheets can react with cellular GSH, resulting in the disintegration of nanosheets to generate plenty of Mn2+ ions for MRI and releases the primers which were adsorbed on the MnO2 nanosheets. Then the rolling circle amplification (RCA) reaction was initiated to amplify the fluorescence signal. In addition, after treatment with GSH, the MnO2 nanosheets were reduced and then most of the fluorescence was recovered. Therefore, this MnO2 nanoprobe exhibits excellent selectivity, suggesting a potential detection platform for analyzing the glutathione level in cells.

Hypoxia is not only the reason of tumor metastasis but also enhances the spread of cancer cells from the original tumor site, which results in cancer recurrence. Herein, we developed a self-assembled RNA hydrogel that efficiently delivered synergistic DNA CpG and short hairpin RNA (shRNA) adjuvants, as well as MnO2 loaded-photodynamic agent chlorine e6 (MnO2@Ce6), and a chemotherapy drug doxorubicin (DOX) into MDA-MB-231cells. The RNA hydrogel consists of one tumour suppressor miRNA (miRNA-205) and one anti-metastatic miRNA (miRNA-182), both of which showed an outstanding effect in synergistically abrogating tumours. The hydrogel would be dissociated by endogenous Dicer enzyme to release loaded therapeutic molecules, and in the meantime induce decomposition of tumor endogenous H2O2 to relieve tumor hypoxia. As a result, a remarkable synergistic therapeutic effect is achieved through the combined chemo-photodynamic therapy, which simultaneously triggers a series of anti-tumor immune responses. Besides, the hydrogel as the carrier which modified aptamer to targeted MDA-MB-231 has the advantages of good biocompatibility and low cytotoxicity. This strategy could be implemented to design any other microRNA (miRNA) as the carrier, combined with other treatment methods to treat human cancer, thereby overcoming the limitations of current cancer therapies.