Local arterial nanoparticle delivery of siRNA for NOX2 knockdown to prevent restenosis in an atherosclerotic rat model
Authors
Li, Jian-mingNewburger, Peter E.
Gounis, Matthew J.
Dargon, Phong
Zhang, Xueqing
Messina, Louis M.
Document Type
Journal ArticlePublication Date
2010-10-17Keywords
AnimalsAtherosclerosis
Genetic Vectors
Hyperplasia
Male
Membrane Glycoproteins
Mice
Models, Animal
NADPH Oxidase
Nanoparticles
Neointima
RNA, Small Interfering
Rats
Rats, Sprague-Dawley
Recurrence
Hematology
Oncology
Pediatrics
Metadata
Show full item recordAbstract
Both atherosclerosis and arterial interventions induce oxidative stress mediated in part by nicotinamide adenine dinucleotide phosphate (NADPH) oxidases that have a pivotal role in the development of neointimal hyperplasia and restenosis. For small interfering RNA (siRNA) targeting of the NOX2 (Cybb) component of the NADPH oxidase to prevent restenosis, gene transfer with viral vectors is effective, but raises safety issues in humans. We developed a new approach using the amino-acid-based nanoparticle HB-OLD7 for local delivery of siRNA targeting NOX2 to the arterial wall. siRNA-nanoparticle complexes were transferred into the regional carotid artery walls after angioplasty in an atherosclerotic rat model. Compared with angioplasty controls, Cybb gene expression (measured by quantitative reverse transcriptase-PCR) in the experimental arterial wall 2 weeks after siRNA was reduced by >87%. The neointima-to-media-area ratio was decreased by >83%, and the lumen-to-whole-artery area ratio was increased by >89%. Vital organs showed no abnormalities and splenic Cybb gene expression showed no detectable change. Thus, local arterial wall gene transfer with HB-OLD7 nanoparticles provides an effective, nonviral system for efficient and safe local gene transfer in a clinically applicable approach to knock down an NADPH oxidase gene. Local arterial knockdown of the Cybb gene significantly inhibited neointimal hyperplasia and preserved the vessel lumen without systemic toxicity.Source
Gene Ther. 2010 Oct;17(10):1279-87. Epub 2010 May 20. Link to article on publisher's websiteDOI
10.1038/gt.2010.69Permanent Link to this Item
http://hdl.handle.net/20.500.14038/43330PubMed ID
20485380Related Resources
Link to article in PubMedae974a485f413a2113503eed53cd6c53
10.1038/gt.2010.69