Interdisciplinary Nanoscience Center (iNANO), Aarhus University, 8000 Aarhus C, Denmark; Department of Molecular Biology and Genetics, Aarhus University, 8000 Aarhus C, Denmark.
Interdisciplinary Nanoscience Center (iNANO), Aarhus University, 8000 Aarhus C, Denmark; Department of Molecular Biology and Genetics, Aarhus University, 8000 Aarhus C, Denmark.
Mol Ther. 2019 Aug 7;27(8):1424-1435. doi: 10.1016/j.ymthe.2019.05.002. Epub 2019 May 15.
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.
白细胞介素-1β（IL-1β）在诱导类风湿关节炎（RA）中发挥核心作用。在本研究中，我们证明了脂质体-聚合物杂化纳米颗粒（FS14-NP）可以有效地将针对 IL-1β 的 siRNA（siIL-1β）递送至巨噬细胞，并有效地抑制胶原抗体诱导的实验性关节炎的发病机制（CAIA 小鼠）。FS14-NP/siIL-1β 在 RAW 264.7 细胞系和腹腔巨噬细胞中的基因沉默效率分别达到了约 70%和 90%。静脉注射 FS14-NP/siRNA 导致 siRNA 在关节炎关节内的巨噬细胞中快速积累。此外，FS14-NP/siIL-1β 治疗降低了关节炎关节中促炎细胞因子的表达，并显著减轻了踝关节肿胀、骨侵蚀和软骨破坏。这些结果表明，FS14-NP/siIL-1β 可能代表一种治疗全身性关节炎和其他炎症性疾病的有效方法。
