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Adv Sci (Weinh). 2019 Jan 15;6(5):1801809. doi: 10.1002/advs.201801809. eCollection 2019 Mar 6.

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

Author information

1
The Third Affiliated Hospital Sun Yat-sen University Guangzhou 510630 China.
2
PCFM Lab of Ministry of Education School of Materials Science and Engineering Sun Yat-sen University Guangzhou 510275 China.
3
Department of Orthopaedics and Traumatology Nanfang Hospital Southern Medical University Guangzhou 510515 China.

Abstract

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.

KEYWORDS:

hepatic stellate cells; liver fibrosis; magnetic resonance imaging visibility; miRNA delivery; nanomedicine; synergistic therapy

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