pPB Peptide-Mediated siRNA-Loaded Stable Nucleic Acid Lipid Nanoparticles on Targeting Therapy of Hepatic Fibrosis

• DOI: 10.1021/acs.molpharmaceut.7b00709
• Publication Date: 2017-11-17T18:11:52Z
• Authors: Zongxiang Jia; Yan Gong; Yufang Pi; Xueying Liu; Lipeng Gao; Liqing Kang; Jing Wang; Fan Yang; Jie Tang; Weiyue Lu; Qinghua Li; Wei Zhang; Zhiqiang Yan; Lei Yu
• Keywords: Hepatic stellate cell; Hepatic fibrosis

Hepatic fibrosis is a necessary process in the development of liver diseases such as hepatic cirrhosis and its complications, which has become serious threat to human health. Currently, antifibrotic drug treatment ineffective, one reason should be lack targeting ability. In this report, polypeptide pPB-modified stable nucleic acid lipid nanoparticles (pPB-SNALPs) were prepared selectively deliver siRNAs against heat shock protein 47 for targeted therapy fibrosis. First, siRNA sequences with high silencing efficiency screened based on transfection efficacy. Then, pPB-SNALPs prepared, showed narrow size distribution diameter range 110–130 nm neutral z-potential 0 mV. As evidenced by vitro vivo study, compared unmodified SNALP, pPB-SNALP increased uptake LX-2 cells primary stellate (HSC) mice HSC vivo. addition, also exhibited an enhanced inhibitory effect TAA-induced gp46 mRNA expression summary, our results demonstrated that effective liver-targeted delivery system. This study could lay good foundation gene