Suppression of MMP-9 expression in brain microvascular endothelial cells (BMVEC) using a gold nanorod (GNR)-siRNA nanoplex

Supriya D. Mahajan, Ravikumar Aalinkeel, Jessica L. Reynolds, Bindukumar Nair, Donald E. Sykes, Adela Bonoiu, Indrajit Roy, Ken Tye Yong, Wing Cheung Law, Earl J. Bergey, Paras N. Prasad, Stanley A. Schwartz

Research output: Journal article publicationJournal articleAcademic researchpeer-review

21 Citations (Scopus)

Abstract

Inhibition of Matrix metalloproteinase-9 (MMP-9) activity using delivery of short interfering RNA (siRNA) molecules to brain microvascular endothelial cells (BMVECs) that constitute the BBB may have a significant impact on reducing the BBB permeability. Gold nano rods (GNRs) can electrostatically bind with MMP-9 siRNA to form a nanoplex and the uptake of this nanoplex by BMVEC cells can result in suppression of MMP-9 expression. The current study explores if this GNR-MMP-9 siRNA nanoplex gene silencing modulates the expression of tight junction (TJ) proteins in the BMVEC. The endothelial TJ's of the BBB play a critical role in controlling cellular traffic into the central nervous system. We hypothesize that silencing of the MMP-9 gene expression in BMVEC will increase the expression of TJ proteins thereby decrease endothelial permeability. Our results showed a significant increase in the gene and protein expression of TJ proteins: ZO-1, Occludin and Claudin-5 in BMVEC cells that were transfected with the GNRs-siRNA-MMP-9 nanoplex suggesting that BBB disruption, which results from loss of TJ function due to MMP-9 activation during neuroinflammation can be prevented by silencing MMP-9 expression.
Original languageEnglish
Pages (from-to)337-355
Number of pages19
JournalImmunological Investigations
Volume41
Issue number4
DOIs
Publication statusPublished - 25 Jun 2012
Externally publishedYes

Keywords

  • BMVEC
  • Gene silencing
  • Gold nano rods
  • MMP-9
  • SiRNA
  • Tight junctions

ASJC Scopus subject areas

  • Immunology

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