Lipidoid-siRNA Nanoparticle-Mediated IL-1 beta Gene Silencing for Systemic Arthritis Therapy in a Mouse Model

Ping Song, Chuanxu Yang, Jesper Skovhus Thomsen, Frederik Dagnaes-Hansen, Maria Jakobsen, Annemarie Bruel, Bent Deleuran, Jorgen Kjems

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Abstract

Interleukin-1 beta (IL-1β) plays a central role in the induction of rheumatoid arthritis (RA). In the present study, we demonstrated that lipidoid-polymer hybrid nanoparticle (FS14-NP) can efficiently deliver siRNA against IL-1β (siIL-1β) to macrophages and effectively suppress the pathogenesis of experimental arthritis induced by collagen antibody (CAIA mice). FS14-NP/siIL-1β achieved approximately 70% and 90% gene-silencing efficiency in the RAW 264.7 cell line and intraperitoneal macrophages, respectively. Intravenous administration of FS14-NP/siRNA led to rapid accumulation of siRNA in macrophages within the arthritic joints. Furthermore, FS14-NP/siIL-1β treatment lowered the expression of pro-inflammatory cytokines in arthritic joints and dramatically attenuated ankle swelling, bone erosion, and cartilage destruction. These results demonstrate that FS14-NP/siIL-1β may represent an effective therapy for systemic arthritis and other inflammatory disorders. Song et al. describe an effective approach for arthritis therapy through delivery of the siRNA against IL-1β by a lipidoid-polymer hybrid nanoparticle (FS14-NP), which is preferentially taken up by activated macrophages that will infiltrate inflammatory sites. This provides the potential for other anti-inflammatory treatments.

OriginalsprogEngelsk
TidsskriftMolecular Therapy
Vol/bind27
Nummer8
Sider (fra-til)1424-1435
Antal sider12
ISSN1525-0016
DOI
StatusUdgivet - 2019

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