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- Title
TNF-α Gene Silencing Using Polymerized siRNA/Thiolated Glycol Chitosan Nanoparticles for Rheumatoid Arthritis.
- Authors
Lee, So Jin; Lee, Aeju; Hwang, Seung Rim; Park, Jong-Sung; Jang, Jiyeon; Huh, Myung Sook; Jo, Dong-Gyu; Yoon, Soo-Young; Byun, Youngro; Kim, Sun Hwa; Kwon, Ick Chan; Youn, Inchan; Kim, Kwangmeyung
- Abstract
Among various proinflammatory cytokines involved in the pathogenesis of rheumatoid arthritis (RA), tumor necrosis factor (TNF)-α 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-α 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-α 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.
- Subjects
GENE silencing; SMALL interfering RNA; RHEUMATOID arthritis; NANOPARTICLES; CHITOSAN; TOMOGRAPHY
- Publication
Molecular Therapy, 2014, Vol 22, Issue 2, p397
- ISSN
1525-0016
- Publication type
Article
- DOI
10.1038/mt.2013.245