Perfluorocarbon Nanoemulsions Enhance Therapeutic siRNA Delivery in the Treatment of Pulmonary Fibrosis

Ling Ding, Siyuan Tang, Weimin Tang, Deanna D. Mosley, Ao Yu, Diptesh Sil, Svetlana Romanova, Kristina L. Bailey, Daren L. Knoell, Todd A. Wyatt, David Oupický

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Local pulmonary administration of therapeutic siRNA represents a promising approach to the treatment of lung fibrosis, which is currently hampered by inefficient delivery. Development of perfluorooctylbromide (PFOB) nanoemulsions as a way of improving the efficiency of pulmonary polycation-based delivery of siRNA is reported. The results show that the polycation/siRNA/PFOB nanoemulsions are capable of efficiently silencing the expression of STAT3 and inhibiting chemokine receptor CXCR4—two validated targets in pulmonary fibrosis. Both in vitro and in vivo results demonstrate that the nanoemulsions improve mucus penetration and facilitate effective cellular delivery of siRNA. Pulmonary treatment of mice with bleomycin-induced pulmonary fibrosis shows strong inhibition of the progression of the disease and significant prolongation of animal survival. Overall, the study points to a promising local treatment strategy of pulmonary fibrosis.

Original languageEnglish (US)
Article number2103676
JournalAdvanced Science
Volume9
Issue number8
DOIs
StatePublished - Mar 15 2022
Externally publishedYes

Keywords

  • CXCR4
  • STAT3
  • idiopathic pulmonary fibrosis
  • perfluorocarbon emulsion
  • pulmonary siRNA delivery

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Chemical Engineering(all)
  • Materials Science(all)
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Engineering(all)
  • Physics and Astronomy(all)

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