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TNF-alpha Gene Silencing Using Polymerized siRNA/Thiolated Glycol Chitosan Nanoparticles for Rheumatoid Arthritis

Authors
Lee, So JinLee, AejuHwang, Seung RimPark, Jong-SungJang, JiyeonHuh, Myung SookJo, Dong-GyuYoon, Soo-YoungByun, YoungroKim, Sun HwaKwon, Ick ChanYoun, InchanKim, Kwangmeyung
Issue Date
2월-2014
Publisher
CELL PRESS
Citation
MOLECULAR THERAPY, v.22, no.2, pp.397 - 408
Indexed
SCIE
SCOPUS
Journal Title
MOLECULAR THERAPY
Volume
22
Number
2
Start Page
397
End Page
408
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/99467
DOI
10.1038/mt.2013.245
ISSN
1525-0016
Abstract
Among various proinflammatory cytokines involved in the pathogenesis of rheumatoid arthritis (RA), tumor necrosis factor (TNF)-alpha, plays a pivotal role in the release of other cytokines and induction of chronic inflammation. Even though siRNA has the therapeutic potential, they have a challenge to be delivered into the target cells because of their poor stability in physiological fluids. Herein, we design a nanocomplex of polymerized siRNA (poly-siRNA) targeting TNF-alpha with thiolated. glycol chitosan (tGC) polymers for the treatment of RA. Poly-siRNA is prepared through self-polymerization of thiol groups at the 5' end of sense and antisense strand of siRNA and encapsulated into tGC polymers, resulting in poly-siRNA-tGC nanoparticles (psi-tGC-NPs) with an average diameter of 370 nm. In the macrophage culture system, psi-tGC-NPs exhibit rapid cellular uptake and excellent in vitro TNF-a gene silencing efficacy. Importantly, psi-tGC-NPs show the high accumulation at the arthritic joint sites in collagen-induced arthritis (CIA) mice. Treatment monitoring data obtained by the matrix metalloproteinase 3 specific nanoprobe and microcomputed tomography show that intravenous injection of psi-tGC-NPs significantly inhibits inflammation and bone erosion in CIA mice, comparable to methotrexate (5 mg/kg). Therefore, the availability of psi-tGC-NP therapy that target specific cytokines may herald new era in the treatment of RA.
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College of Medicine > Department of Medical Science > 1. Journal Articles
Graduate School > KU-KIST Graduate School of Converging Science and Technology > 1. Journal Articles

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