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

TY - JOUR

T1 - Lipidoid-siRNA Nanoparticle-Mediated IL-1 beta Gene Silencing for Systemic Arthritis Therapy in a Mouse Model

AU - Song, Ping

AU - Yang, Chuanxu

AU - Thomsen, Jesper Skovhus

AU - Dagnaes-Hansen, Frederik

AU - Jakobsen, Maria

AU - Bruel, Annemarie

AU - Deleuran, Bent

AU - Kjems, Jorgen

PY - 2019/8/7

Y1 - 2019/8/7

N2 - 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.

AB - 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.

KW - CATIONIC LIPIDS

KW - CYTOKINES

KW - DELIVERY

KW - DEXAMETHASONE

KW - DISEASE

KW - INFLAMMATION

KW - MECHANISMS

KW - NANOMATERIALS

KW - RHEUMATOID-ARTHRITIS

KW - TNF-ALPHA

UR - https://www.scopus.com/pages/publications/85066244680

U2 - 10.1016/j.ymthe.2019.05.002

DO - 10.1016/j.ymthe.2019.05.002

M3 - Journal article

C2 - 31153827

SN - 1525-0016

VL - 27

SP - 1424

EP - 1435

JO - Molecular Therapy

JF - Molecular Therapy

IS - 8

ER -