Notch1 targeting siRNA delivery nanoparticles for rheumatoid arthritis therapy
- Authors
- Kim, Min Ju; Park, Jong-Sung; Lee, So Jin; Jang, Jiyeon; Park, Jin Su; Back, Seung Hyun; Bahn, Gahee; Park, Jae Hyung; Kang, Young Mo; Kim, Sun Hwa; Kwon, Ick Chan; Jo, Dong-Gyu; Kim, Kwangmeyung
- Issue Date
- 28-10월-2015
- Publisher
- ELSEVIER SCIENCE BV
- Keywords
- Notch1 targeting siRNA; siRNA delivery; Nanoparticles; Rheumatoid arthritis
- Citation
- JOURNAL OF CONTROLLED RELEASE, v.216, pp.140 - 148
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF CONTROLLED RELEASE
- Volume
- 216
- Start Page
- 140
- End Page
- 148
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/92154
- DOI
- 10.1016/j.jconrel.2015.08.025
- ISSN
- 0168-3659
- Abstract
- Notch pathway plays a pivotal role in synoviocytes involved in progression of rheumatoid arthritis (RA). Herein, we designed the Notch1 targeting siRNA delivery nanoparticles (siRNA-NPs) in order to confirm the anti-inflammatory effect in collagen-induced arthritis (CIA) model. The siRNA-NPs were successfully produced by encapsulating polymerized siRNA (poly-siRNA) into thiolated glycol chitosan (tGC) nanoparticles in aqueous condition. The in vitro Notch1 inhibition of siRNA-NPs in murine macrophage cell (RAW264.7) was confirmed using confocal microscopy and real time PCR. Fluorescently labeled siRNA-NPs were successfully transfected in RAW264.7 and modulated the expression of Notch1 in mRNA level. For in vivo study, siRNA-NPs exhibited the higher targeting efficiency in the arthritic joins of CIA mice, confirmed by the near-infrared fluorescence (NIRF) imaging. Furthermore, inhibition of Notch1 with siRNA-NPs resulted in retarded progression of inflammation, bone erosion, and cartilage damage in CIA mice. Novel Notch1 targeting siRNA delivery system of siRNA-NPs showed effective RA treatment by suppressing Notch1 signaling pathway without undesirable severe toxicity. Thus, Notch1 inhibiting siRNA-NPs demonstrated the great potential in RA therapeutics that was hard to be achieved using conventional drugs. (C) 2015 Elsevier B.V. All rights reserved.
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Collections - Graduate School > KU-KIST Graduate School of Converging Science and Technology > 1. Journal Articles
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