Open AccessSynergistic MicroRNA Therapy in Liver Fibrotic Rat Using MRI‐Visible Nanocarrier Targeting Hepatic Stellate Cells
Author(s) -
Wu Jun,
Huang Jinsheng,
Kuang Sichi,
Chen Jingbiao,
Li Xiaoxia,
Chen Bin,
Wang Jin,
Cheng Du,
Shuai Xintao
Publication year - 2019
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.201801809
Subject(s) - nanocarriers , hepatic stellate cell , microrna , cancer research , genetic enhancement , hepatic fibrosis , in vivo , fibrosis , drug delivery , medicine , chemistry , pharmacology , pathology , biology , biochemistry , drug , gene , microbiology and biotechnology , organic chemistry
Liver fibrosis, as one of the leading causes of liver‐related morbidity and mortality, has no Food and Drug Administration (FDA)‐approved antifibrotic therapy yet. Although microRNA‐29b (miRNA‐29b) and microRNA‐122 (miRNA‐122) have great potential in treating liver fibrosis via regulating profibrotic genes in hepatic stellate cells (HSCs), it is still a challenge to achieve a HSC‐targeted and meanwhile noninvasively trackable delivery of miRNAs in vivo. Herein, a pH‐sensitive and vitamin A (VA)‐conjugated copolymer VA–polyethylene glycol–polyethyleneimine–poly( N ‐( N ′, N ′‐diisopropylaminoethyl)‐ co ‐benzylamino) aspartamide (T‐PBP) is synthesized and assembled into superparamagnetic iron oxide (SPIO)‐decorated cationic micelle for miRNA delivery. The T‐PBP micelle efficiently transports the miRNA‐29b and miRNA‐122 to HSC in a magnetic resonance imaging‐visible manner, resulting in a synergistic antifibrosis effect via downregulating the expression of fibrosis‐related genes, including collagen type I alpha 1, α‐smooth muscle actin, and tissue inhibitor of metalloproteinase 1. Consequently, the HSC‐targeted combination therapy with miRNA‐29b and miRNA‐122 demonstrates a prominent antifibrotic efficacy in terms of improving liver function and relieving hepatic fibrosis.