Inhibition of monocyte adhesion to brain-derived endothelial cells by dual functional RNA chimeras

Jing Hu, Feng Xiao, Xin Hao, Shuhua Bai, Jiukuan Hao

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Because adhesion of leukocytes to endothelial cells is the first step of vascular-neuronal inflammation, inhibition of adhesion and recruitment of leukocytes to vascular endothelial cells will have a beneficial effect on neuroinflammatory diseases. In this study, we used the pRNA of bacteriophage phi29 DNA packaging motor to construct a novel RNA nanoparticle for specific targeting to transferrin receptor (TfR) on the murine brain-derived endothelial cells (bEND5) to deliver ICAM-1 siRNA. This RNA nanoparticle (FRS-NPs) contained a FB4 aptamer targeting to TfR and a siRNA moiety for silencing the intercellular adhesion molecule-1 (ICAM-1). Our data indicated that this RNA nanoparticle was delivered into murine brain-derived endothelial cells. Furthermore, the siRNA was released from the FRS-NPs in the cells and knocked down ICAM-1 expression in the TNF-α-stimulated cells and in the cells under oxygen-glucose deprivation/reoxygenation (OGD/R) condition. The functional end points of the study indicated that FRS-NPs significantly inhibited monocyte adhesion to the bEND5 cells induced by TNF-α and OGD/R. In conclusion, our approach using RNA nanotechnology for siRNA delivery could be potentially applied for inhibition of inflammation in ischemic stroke and other neuroinflammatory diseases, or diseases affecting endothelium of vasculature.

Original languageEnglish (US)
Pages (from-to)e209
JournalMolecular Therapy - Nucleic Acids
Volume3
DOIs
StatePublished - 2014

Keywords

  • Blood-brain barrier
  • Endothelial cell
  • Inflammation
  • Intercellular adhesion molecule-1
  • Ischemia
  • Oxygen-glucose deprivation
  • RNA nanotechnology
  • SiRNA
  • Transferrin receptor

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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