Synergistic MicroRNA Therapy in Liver Fibrotic Rat Using MRI‐Visible Nanocarrier Targeting Hepatic Stellate Cells

• DOI: 10.1002/advs.201801809
• Publication Date: 2019-01-15T14:35:52Z
• Authors: Jun Wu; Jinsheng Huang; Sichi Kuang; Jingbiao Chen; Xiaoxia Li; Bin Chen; Jin Wang; Du Cheng; Xintao Shuai
• Keywords: Nanocarriers; Hepatic stellate cell; Hepatic fibrosis

Abstract Liver fibrosis, as one of the leading causes liver‐related morbidity and mortality, has no Food Drug Administration (FDA)‐approved antifibrotic therapy yet. Although microRNA‐29b (miRNA‐29b) microRNA‐122 (miRNA‐122) have great potential in treating liver fibrosis via regulating profibrotic genes hepatic stellate cells (HSCs), it is still a challenge to achieve HSC‐targeted meanwhile noninvasively trackable delivery miRNAs vivo. Herein, pH‐sensitive vitamin A (VA)‐conjugated copolymer VA–polyethylene glycol–polyethyleneimine–poly( N ‐( ′, ′‐diisopropylaminoethyl)‐ co ‐benzylamino) aspartamide (T‐PBP) synthesized assembled into superparamagnetic iron oxide (SPIO)‐decorated cationic micelle for miRNA delivery. The T‐PBP efficiently transports miRNA‐29b miRNA‐122 HSC magnetic resonance imaging‐visible manner, resulting synergistic antifibrosis effect downregulating expression fibrosis‐related genes, including collagen type I alpha 1, α‐smooth muscle actin, tissue inhibitor metalloproteinase 1. Consequently, combination with demonstrates prominent efficacy terms improving function relieving fibrosis.