Simple and rational design of a polymer nano-platform for high performance of HCV related miR-122 reduction in the liver

Abstract

microRNA-122 (miR-122) is a kind of non-coding RNA expressed specifically in the liver and accumulating evidence elucidates its relationship with HCV virus replication. The utilization of anti-miRNA oligonucleotide (antimiR) offers tremendous potential for future HCV infection therapy. However, multiple existing problems, such as targeting and stability, impede in vivo application of antimiR. To overcome them, we synthesized monomethoxy (polyethylene glycol)-poly (D,L lactide-co-glycolide)-poly (L-lysine) (mPEG-b-PLGA-b-PLL) materials to deliver miR-122 antagomir (AN), and formed stable and well-distributed AN-loaded mPEG-b-PLGA-b-PLL nanoparticles (NP-AN). NP-AN showed a high degree of miR-122 inhibition after 72 h in vitro. In vivo results showed an NP-AN “leak” through a hepatic sinusoid to reach hepatocytes and over 90% reduction of miR-122 after being injected with NP-AN for 72 h. Besides, the inhibition of miR-122 lasted for 28 days with limited dosage in vivo. This study strongly suggests that the silencing of miR-122 was enhanced and the reduction of miR-122 expression could be extended by utilizing an mPEG-b-PLGA-b-PLL nano-platform, which potentially facilitate further studies on miRNA function loss and related RNAi therapy for HCV infection.