title: Suppression of MMP-9 expression in brain microvascular endothelial cells (BMVEC) using a gold nanorod (GNR)-siRNA nanoplex.
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.
authors.affiliation: Department of Medicine, Division of Allergy, Immunology, and Rheumatology, University at Buffalo, The State University of New York, Innovation Center, Buffalo, New York 14203, USA. smahajan@buffalo.edu
authors.forename: Supriya D
authors.initials: SD
authors.lastname: Mahajan
authors.forename: Ravikumar
authors.initials: R
authors.lastname: Aalinkeel
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Reynolds
authors.forename: Bindukumar
authors.initials: B
authors.lastname: Nair
authors.forename: Donald E
authors.initials: DE
authors.lastname: Sykes
authors.forename: Adela
authors.initials: A
authors.lastname: Bonoiu
authors.forename: Indrajit
authors.initials: I
authors.lastname: Roy
authors.forename: Ken-Tye
authors.initials: KT
authors.lastname: Yong
authors.forename: Wing-Cheung
authors.initials: WC
authors.lastname: Law
authors.forename: Earl J
authors.initials: EJ
authors.lastname: Bergey
authors.forename: Paras N
authors.initials: PN
authors.lastname: Prasad
authors.forename: Stanley A
authors.initials: SA
authors.lastname: Schwartz
mesh_terms: D001921:Brain / Q000378:metabolism*; D002470:Cell Survival; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D055806:Microvessels / Q000166:cytology; D043942:Nanotubes / Q000737:chemistry / Q000648:ultrastructure; D010316:Particle Size; D034741:RNA, Small Interfering / Q000737:chemistry / Q000378:metabolism*; D055672:Static Electricity; D019108:Tight Junctions / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D034741:RNA, Small Interfering; D020780:Matrix Metalloproteinase 9