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 2024-01-20T06:00:59Z 2024-01-20T06:00:59Z 2021-09-04 2015-10-28 0168-3659 https://pubs.kist.re.kr/handle/201004/124867 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. English ELSEVIER SCIENCE BV COLLAGEN-INDUCED ARTHRITIS GLYCOL CHITOSAN NANOPARTICLES POLYMERIZED SIRNA INTRACELLULAR DOMAIN SYSTEMIC DELIVERY CELLULAR UPTAKE ANGIOGENESIS PATHOGENESIS INFLAMMATION ACTIVATION Notch1 targeting siRNA delivery nanoparticles for rheumatoid arthritis therapy Article 10.1016/j.jconrel.2015.08.025 1 JOURNAL OF CONTROLLED RELEASE, v.216, pp.140 - 148 JOURNAL OF CONTROLLED RELEASE 216 140 148 scie scopus 000363480600015 2-s2.0-84940199341 Chemistry, Multidisciplinary Pharmacology & Pharmacy Chemistry Pharmacology & Pharmacy Article COLLAGEN-INDUCED ARTHRITIS GLYCOL CHITOSAN NANOPARTICLES POLYMERIZED SIRNA INTRACELLULAR DOMAIN SYSTEMIC DELIVERY CELLULAR UPTAKE ANGIOGENESIS PATHOGENESIS INFLAMMATION ACTIVATION Notch1 targeting siRNA siRNA delivery Nanoparticles Rheumatoid arthritis