Pulmonary delivery of polyplexes for combined PAI-1 gene silencing and CXCR4 inhibition to treat lung fibrosis

Ling Ding, Chenfei Zhu, Fei Yu, Pengkai Wu, Gang Chen, Aftab Ullah, Kaikai Wang, Minjie Sun, Jing Li, David Oupický

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

This report describes the development of polyplexes based on CXCR4-inhibiting poly(ethylenimine) derivative (PEI-C) for pulmonary delivery of siRNA to silence plasminogen activator inhibitor-1 (siPAI-1) as a new combination treatment of pulmonary fibrosis (PF). Safety and delivery efficacy of the PEI-C/siPAI-1 polyplexes was investigated in vitro in primary lung fibroblasts isolated from mice with bleomycin-induced PF. Biodistribution analysis following intratracheal administration of fluorescently labeled polyplexes showed prolonged retention in the lungs. Treatment of mice with bleomycin-induced PF using the PEI-C/siPAI-1 polyplexes resulted in a significant down-regulation of the PAI-1 expression and decreased collagen deposition in the lung. The results of this study provide first evidence of the potential benefits of combined inhibition of CXCR4 and PAI-1 in the pulmonary treatment of PF.

Original languageEnglish (US)
Pages (from-to)1765-1776
Number of pages12
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume14
Issue number6
DOIs
StatePublished - Aug 2018

Keywords

  • CXCR4
  • Intratracheal administration
  • PAI-1
  • Pulmonary fibrosis
  • siRNA

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science

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