2. Academic Validation
  3. pPB Peptide-Mediated siRNA-Loaded Stable Nucleic Acid Lipid Nanoparticles on Targeting Therapy of Hepatic Fibrosis

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

  • Mol Pharm. 2018 Jan 2;15(1):53-62. doi: 10.1021/acs.molpharmaceut.7b00709.
Zongxiang Jia 1,  Yan Gong 2,  Yufang Pi 1,  Xueying Liu 1,  Lipeng Gao 1,  Liqing Kang 1,  Jing Wang 1,  Fan Yang 1,  Jie Tang 1,  Weiyue Lu 3,  Qinghua Li 4,  Wei Zhang 5,  Zhiqiang Yan 1,  Lei Yu 1
Affiliations

Affiliations

  • 1 Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University , Shanghai 200062, P.R. China.
  • 2 Department of Geriatrics, Huashan Hospital, Fudan University , Shanghai 200040, P.R. China.
  • 3 Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery, Fudan University, Ministry of Education , Shanghai 201203, P.R. China.
  • 4 Department of Hepatology and Pancreatology, Shanghai East Hospital, Tongji University , Shanghai 200120, P.R. China.
  • 5 Key Laboratory of Brain Functional Genomics, Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, School of Life Science, East China Normal University , Shanghai 200062, P.R. China.
PMID: 29148802 DOI: 10.1021/acs.molpharmaceut.7b00709
Abstract

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

Keywords

hepatic fibrosis; pPB; siRNA; stable nucleic acid lipid nanoparticles (SNALPs); targeting therapy.

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