Notch1 targeting siRNA delivery nanoparticles for rheumatoid arthritis therapy

作者：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

来源：Journal of Controlled Release, 2015, 216: 140-148.

DOI：10.1016/j.jconrel.2015.08.025

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

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.

• 出版日期2015-10-28