Notch1 targeting siRNA delivery nanoparticles for rheumatoid arthritis therapy

Min Ju Kim, Jong Sung Park, So Jin Lee, Jiyeon Jang, Jin Su Park, Seung Hyun Back, Gahee Bahn, Jae Hyung Park, Young Mo Kang, Sun Hwa Kim, Ick Chan Kwon, Dong Gyu Jo, Kwang Meyung Kim

Research output: Contribution to journalArticle

34 Citations (Scopus)

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 (RAW 264.7) was confirmed using confocal microscopy and real time PCR. Fluorescently labeled siRNA-NPs were successfully transfected in RAW 264.7 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.

Original languageEnglish
Pages (from-to)140-148
Number of pages9
JournalJournal of Controlled Release
Volume216
DOIs
Publication statusPublished - 2015 Oct 28

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Keywords

  • Nanoparticles
  • Notch1 targeting siRNA
  • Rheumatoid arthritis
  • siRNA delivery

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Kim, M. J., Park, J. S., Lee, S. J., Jang, J., Park, J. S., Back, S. H., Bahn, G., Park, J. H., Kang, Y. M., Kim, S. H., Kwon, I. C., Jo, D. G., & Kim, K. M. (2015). Notch1 targeting siRNA delivery nanoparticles for rheumatoid arthritis therapy. Journal of Controlled Release, 216, 140-148. https://doi.org/10.1016/j.jconrel.2015.08.025