1. Lipidoid-siRNA Nanoparticle-Mediated IL-1β Gene Silencing for Systemic Arthritis Therapy in a Mouse Model
- Author
-
Annemarie Brüel, Bent Deleuran, Jørgen Kjems, Chuanxu Yang, Frederik Dagnæs-Hansen, Ping Song, Maria Jakobsen, and Jesper Skovhus Thomsen
- Subjects
Interleukin-1beta ,Fluorescent Antibody Technique ,Gene Expression ,Arthritis ,DISEASE ,Arthritis, Rheumatoid ,Pathogenesis ,Mice ,0302 clinical medicine ,Drug Discovery ,RNA, Small Interfering ,0303 health sciences ,Molecular Structure ,Gene Transfer Techniques ,TNF-ALPHA ,Lipids ,DEXAMETHASONE ,030220 oncology & carcinogenesis ,Rheumatoid arthritis ,Cytokines ,Molecular Medicine ,Original Article ,Inflammation Mediators ,Experimental arthritis ,Bone and Bones ,MECHANISMS ,DELIVERY ,03 medical and health sciences ,INFLAMMATION ,Genetics ,medicine ,Animals ,Gene silencing ,Gene Silencing ,Beta (finance) ,Molecular Biology ,030304 developmental biology ,NANOMATERIALS ,Pharmacology ,business.industry ,Macrophages ,CYTOKINES ,Genetic Therapy ,CATIONIC LIPIDS ,medicine.disease ,Arthritis, Experimental ,RHEUMATOID-ARTHRITIS ,Disease Models, Animal ,RAW 264.7 Cells ,Arthritis therapy ,Cell culture ,Cancer research ,Nanoparticles ,business ,Biomarkers - 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.
- Published
- 2019
- Full Text
- View/download PDF