Self-Assembled saRNA Delivery System Based on Rolling Circle Transcription for Aptamer-Targeting Cancer Therapy.

With the capacity of gene promotion, RNA activation (RNAa) has been supposed to be a powerful technique in the field of biomedicine, especially in an antitumor aspect. However, one of the pressing challenges for clinical application is how to efficiently deliver therapeutic probes to cancer. Herein, we synthesized a carrier through rolling circle transcription (RCT) to deliver p21 saRNA with high loading rate and targeting capacity. This carrier could be condensed from a micron dimension to about 200 nm by polyethylenimine (PEI). In addition, the trait of robust tumor targeting and improved cytotoxicity was demonstrated when the aptamer was modified through layer-by-layer self-assembly. Moreover, the 4-fold activation of the p21 gene could be obviously detected in a targeting group. Meanwhile, the cell apoptosis induced by p21 promotion was also exhibited, which indicated that this highly efficient saRNA delivery carrier had a specific antitumor effect and could reduce side effects to normal cells. Therefore, this delivery system had the potential to be used in RNAa applications and cancer-targeted treatment.