Inhibition of Monocyte Adhesion to Brain-Derived Endothelial Cells by Dual Functional RNA Chimeras
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 ph...
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2014-01-01
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doaj-90a0e3ea0ac94ff7a8c06acb5ce3c8e92020-11-24T22:15:57ZengElsevierMolecular Therapy: Nucleic Acids2162-25312014-01-013C10.1038/mtna.2014.60Inhibition of Monocyte Adhesion to Brain-Derived Endothelial Cells by Dual Functional RNA ChimerasJing Hu0Feng Xiao1Xin Hao2Shuhua Bai3Jiukuan Hao4Division of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, Ohio, USADepartment of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX , USADepartment of Biological Sciences, McMicken College of Arts & Sciences, University of Cincinnati, Cincinnati, Ohio, USADepartment of Basic Pharmaceutical Sciences, School of Pharmacy, Husson University, Bangor, Maine, USADivision of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, Ohio, USABecause 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.http://www.sciencedirect.com/science/article/pii/S2162253116303481blood–brain barrierendothelial cellinflammationintercellular adhesion molecule-1ischemiaRNA nanotechnologysiRNAtransferrin receptoroxygen-glucose deprivation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jing Hu Feng Xiao Xin Hao Shuhua Bai Jiukuan Hao |
spellingShingle |
Jing Hu Feng Xiao Xin Hao Shuhua Bai Jiukuan Hao Inhibition of Monocyte Adhesion to Brain-Derived Endothelial Cells by Dual Functional RNA Chimeras Molecular Therapy: Nucleic Acids blood–brain barrier endothelial cell inflammation intercellular adhesion molecule-1 ischemia RNA nanotechnology siRNA transferrin receptor oxygen-glucose deprivation |
author_facet |
Jing Hu Feng Xiao Xin Hao Shuhua Bai Jiukuan Hao |
author_sort |
Jing Hu |
title |
Inhibition of Monocyte Adhesion to Brain-Derived Endothelial Cells by Dual Functional RNA Chimeras |
title_short |
Inhibition of Monocyte Adhesion to Brain-Derived Endothelial Cells by Dual Functional RNA Chimeras |
title_full |
Inhibition of Monocyte Adhesion to Brain-Derived Endothelial Cells by Dual Functional RNA Chimeras |
title_fullStr |
Inhibition of Monocyte Adhesion to Brain-Derived Endothelial Cells by Dual Functional RNA Chimeras |
title_full_unstemmed |
Inhibition of Monocyte Adhesion to Brain-Derived Endothelial Cells by Dual Functional RNA Chimeras |
title_sort |
inhibition of monocyte adhesion to brain-derived endothelial cells by dual functional rna chimeras |
publisher |
Elsevier |
series |
Molecular Therapy: Nucleic Acids |
issn |
2162-2531 |
publishDate |
2014-01-01 |
description |
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. |
topic |
blood–brain barrier endothelial cell inflammation intercellular adhesion molecule-1 ischemia RNA nanotechnology siRNA transferrin receptor oxygen-glucose deprivation |
url |
http://www.sciencedirect.com/science/article/pii/S2162253116303481 |
work_keys_str_mv |
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