Notch1 targeting siRNA delivery nanoparticles for rheumatoid arthritis therapy
- Notch1 targeting siRNA delivery nanoparticles for rheumatoid arthritis therapy
- 김민주; Jong-Sung Park; 이소진; Jiyeon Jang; Jin Su Park; Seung Hyun Back; Gahee Bahn; Jae Hyung Park; Young Mo Kang; 김선화; 권익찬; Dong-Gyu Jo; 김광명
- Notch1 targeting siRNA; siRNA delivery; Nanoparticles; Rheumatoid arthritis
- Issue Date
- Journal of controlled release
- VOL 216, NO 28, 140-148
- 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.
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