Leukocyte recruitment plays a key role in chronic inflammatory diseases such as cardiovascular disease, rheumatoid arthritis, and cancer. Leukocyte rolling and arrest are mediated in part by the temporally-regulated surface expression of vascular cell adhesion molecule-1 (VCAM1) on endothelial cells (ECs). In this paper, we engineered a pH-responsive vehicle comprised of 30 mol% dimethylaminoethyl methacrylate (30D) and 70 mol% hydroxyethyl methacrylate (70H) to encapsulate, protect, and deliver VCAM1 small interfering RNA (siRNA). The ability of siRNA to reduce VCAM1 gene expression is in direct opposition to its activation by cytokines. At 12 h post-activation, VCAM1 gene knockdown was 90.1 ± 7.5% when delivered via 30D/70H nanoparticles, which was on par with a leading commercial transfection agent. This translated into a 68.8 ± 6.7% reduction in the surface density of VCAM1 on cytokine-activated ECs. The pH-responsive delivery of VCAM1 siRNA efficiently reduced temporal surface protein expression, which may be used to avert leukocyte recruitment.
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Similar content being viewed by others Explore related subjectsDiscover the latest articles and news from researchers in related subjects, suggested using machine learning. AbbreviationsVascular cell adhesion molecule-1
Endothelial cells
30 mol% dimethylaminoethyl methacrylate
70 mol% hydroxyethyl methacrylate
Small interfering RNA
Intercellular cell adhesion molecule-1
Tumor necrosis factor-α
Dimethylaminoethyl methacrylate
Hydroxyethyl methacrylate
Interleukin 1α
Transmission electron microscopy
Platelet endothelial cell adhesion molecule or cluster of differentiation 31
Tetraethylene glycol dimethacrylate
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This work was funded in part by the National Science Foundation under NSF Award No. DMR 1406271. This work was performed in part at the Center for Nanoscale Systems (CNS), a member of the National Nanotechnology Infrastructure Network (NNIN), which is supported by NSF Award No. ECS-0335765. CNS is part of the Faculty of Arts and Sciences at Harvard University.
Author information Author notesTheodore T. Ho
Present address: The Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Department of Medicine, Division of Hematology/Oncology, University of California San Francisco, San Francisco, CA, 94143, USA
Jin-Oh You
Present address: Department of Engineering Chemistry, Chungbuk National University, Cheongju, 361-763, Republic of Korea
Debra T. Auguste
Present address: Grove School of Engineering, The City College of New York, 160 Convent Avenue, New York, NY, 10031, USA
School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, 02138, USA
Theodore T. Ho, Jin-Oh You & Debra T. Auguste
Vascular Biology Program, Boston Children’s Hospital, Harvard Medical School, Boston, MA, 02115, USA
Debra T. Auguste
Correspondence to Debra T. Auguste.
Additional informationAssociate Editor Michael Gower oversaw the review of this article.
Electronic Supplementary MaterialBelow is the link to the electronic supplementary material.
About this article Cite this articleHo, T.T., You, JO. & Auguste, D.T. siRNA Delivery Impedes the Temporal Expression of Cytokine-Activated VCAM1 on Endothelial Cells. Ann Biomed Eng 44, 895–902 (2016). https://doi.org/10.1007/s10439-015-1364-x
Received: 24 February 2015
Accepted: 11 June 2015
Published: 23 June 2015
Issue Date: April 2016
DOI: https://doi.org/10.1007/s10439-015-1364-x
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