Notch1 targeting siRNA delivery nanoparticles for rheumatoid arthritis therapy.
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.
Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul 136-791, Republic of Korea; KU-KIST School, Korea University, Anam-dong, Seongbuk-gu, Seoul 136-701, Republic of Korea.
Min Ju
MJ
Kim
School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
Jong-Sung
JS
Park
Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul 136-791, Republic of Korea.
So Jin
SJ
Lee
School of Chemical Engineering, Sungkyunkwan University, Suwan 440-746, Republic of Korea.
Jiyeon
J
Jang
School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
Jin Su
JS
Park
School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
Seung Hyun
SH
Back
School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
Gahee
G
Bahn
School of Chemical Engineering, Sungkyunkwan University, Suwan 440-746, Republic of Korea.
Jae Hyung
JH
Park
School of Medicine, Kyungpook National University, Daegu 700-422, Republic of Korea.
Young Mo
YM
Kang
Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul 136-791, Republic of Korea.
Sun Hwa
SH
Kim
Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul 136-791, Republic of Korea; KU-KIST School, Korea University, Anam-dong, Seongbuk-gu, Seoul 136-701, Republic of Korea.
Ick Chan
IC
Kwon
School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea. Electronic address: jodg@skku.edu.
Dong-Gyu
DG
Jo
Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul 136-791, Republic of Korea. Electronic address: kim@kist.re.kr.
Kwangmeyung
K
Kim
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D001842:Bone and Bones / Q000473:pathology; D002356:Cartilage / Q000473:pathology; D048271:Chitosan; D003094:Collagen; D018450:Disease Progression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D051379:Mice; D053758:Nanoparticles; D000067996:RAW 264.7 Cells; D034741:RNA, Small Interfering / Q000494:pharmacology*; D051881:Receptor, Notch1 / Q000187:drug effects*; D014162:Transfection
C497762:Notch1 protein, mouse; D034741:RNA, Small Interfering; D051881:Receptor, Notch1; D003094:Collagen; D048271:Chitosan
Nanoparticles; Notch1 targeting siRNA; Rheumatoid arthritis; siRNA delivery