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

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Lipidoid-siRNA Nanoparticle-Mediated IL-1 beta Gene Silencing for Systemic Arthritis Therapy in a Mouse Model. / Song, Ping; Yang, Chuanxu; Thomsen, Jesper Skovhus; Dagnaes-Hansen, Frederik; Jakobsen, Maria; Bruel, Annemarie; Deleuran, Bent; Kjems, Jorgen.

In: Molecular Therapy, Vol. 27, No. 8, 2019, p. 1424-1435.

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@article{ea2e4142b2eb44179d4a0eb25f3ded8c,
title = "Lipidoid-siRNA Nanoparticle-Mediated IL-1 beta Gene Silencing for Systemic Arthritis Therapy in a Mouse Model",
abstract = "Interleukin-1 beta (IL-1 beta) 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-1 beta (siIL-1 beta) to macrophages and effectively suppress the pathogenesis of experimental arthritis induced by collagen antibody (CAIA mice). FS14-NP/siIL-1 beta achieved approximately 70{\%} and 90{\%} genesilencing 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/siIL1 beta 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-1 beta may represent an effective therapy for systemic arthritis and other inflammatory disorders.",
keywords = "RHEUMATOID-ARTHRITIS, TNF-ALPHA, CATIONIC LIPIDS, DELIVERY, DISEASE, INFLAMMATION, MECHANISMS, CYTOKINES, DEXAMETHASONE, NANOMATERIALS",
author = "Ping Song and Chuanxu Yang and Thomsen, {Jesper Skovhus} and Frederik Dagnaes-Hansen and Maria Jakobsen and Annemarie Bruel and Bent Deleuran and Jorgen Kjems",
year = "2019",
doi = "10.1016/j.ymthe.2019.05.002",
language = "English",
volume = "27",
pages = "1424--1435",
journal = "Molecular Therapy",
issn = "1525-0016",
publisher = "Nature Publishing Group",
number = "8",

}

RIS

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

Y1 - 2019

N2 - Interleukin-1 beta (IL-1 beta) 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-1 beta (siIL-1 beta) to macrophages and effectively suppress the pathogenesis of experimental arthritis induced by collagen antibody (CAIA mice). FS14-NP/siIL-1 beta achieved approximately 70% and 90% genesilencing 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/siIL1 beta 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-1 beta may represent an effective therapy for systemic arthritis and other inflammatory disorders.

AB - Interleukin-1 beta (IL-1 beta) 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-1 beta (siIL-1 beta) to macrophages and effectively suppress the pathogenesis of experimental arthritis induced by collagen antibody (CAIA mice). FS14-NP/siIL-1 beta achieved approximately 70% and 90% genesilencing 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/siIL1 beta 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-1 beta may represent an effective therapy for systemic arthritis and other inflammatory disorders.

KW - RHEUMATOID-ARTHRITIS

KW - TNF-ALPHA

KW - CATIONIC LIPIDS

KW - DELIVERY

KW - DISEASE

KW - INFLAMMATION

KW - MECHANISMS

KW - CYTOKINES

KW - DEXAMETHASONE

KW - NANOMATERIALS

U2 - 10.1016/j.ymthe.2019.05.002

DO - 10.1016/j.ymthe.2019.05.002

M3 - Journal article

VL - 27

SP - 1424

EP - 1435

JO - Molecular Therapy

JF - Molecular Therapy

SN - 1525-0016

IS - 8

ER -