ArticleMolecular therapy : the journal of the American Society of Gene Therapy2009
Chitosan/siRNA nanoparticle-mediated TNF-alpha knockdown in peritoneal macrophages for anti-inflammatory treatment in a murine arthritis model.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
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Who cites it
90 citing papers in PubMed, 296 citations in OpenAlex.
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- Nucleic Acid-based Therapy in Effective Management of Rheumatoid Arthritis.Current pharmaceutical design · 2025Review
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- Therapeutic Potential of Nanocarriers in the Management of Rheumatoid Arthritis.Current rheumatology reviews · 2025Review
- Nanocarrier-based delivery of siRNA therapeutics in rheumatoid arthritis: immune mechanisms and translational perspectives.Frontiers in immunology · 2025Review
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- Multilevel chitosan-gelatin particles loaded with P4HA1 siRNA suppress glioma development.Drug delivery and translational research · 2024Article
- The emerging potential of siRNA nanotherapeutics in treatment of arthritis.Asian journal of pharmaceutical sciences · 2023Review
- Nanoparticles targeting monocytes and macrophages as diagnostic and therapeutic tools for autoimmune diseases.Heliyon · 2023Review
- Effect of nanoparticle size on their distribution and retention in chronic inflammation sites.Discover nano · 2023Article
- Research Advances in Nucleic Acid Delivery System for Rheumatoid Arthritis Therapy.Pharmaceutics · 2023Review
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- SRA inhibition improves antitumor potency of antigen-targeted chaperone vaccine.Frontiers in immunology · 2023Article
- Immunomodulation in age-related disorders and nanotechnology interventions.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology · 2023Review
- Current and future outlook of loaded components in hydrogel composites for the treatment of chronic diabetic ulcers.Frontiers in bioengineering and biotechnology · 2023Review
30 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Secretion of tumor necrosis factor-alpha (TNF-alpha) by macrophages plays a predominant role in the development and progression of rheumatoid arthritis. We demonstrate that knockdown of TNF-alpha expression in systemic macrophages by intraperitoneal (i.p.) administration of chitosan/small interfering RNA (siRNA) nanoparticles in mice downregulates systemic and local inflammation. Chitosan nanoparticles containing an unmodified anti-TNF-alpha Dicer-substrate siRNA (DsiRNA) mediated TNF-alpha knockdown (approximately 66%) in primary peritoneal macrophages in vitro. The presence of Cy3-labeled nanoparticles within peritoneal macrophages and specific TNF-alpha knockdown (approximately 44%) with TNF-alpha siRNA after i.p. injection supports our therapeutic approach. Downregulation of TNF-alpha-induced inflammatory responses arrested joint swelling in collagen-induced arthritic (CIA) mice dosed i.p. with anti-TNF-alpha DsiRNA nanoparticles. The use of 2'-O-Me-modified DsiRNA resulted in the lowest arthritic scores and correlated with reduced type I interferon (IFN) activation in macrophages in vivo compared with unmodified DsiRNA. Histological analysis of joints revealed minimal cartilage destruction and inflammatory cell infiltration in anti-TNF-alpha-treated mice. The onset of arthritis could be delayed using a prophylactic dosing regime. This work demonstrates nanoparticle-mediated TNF-alpha knockdown in peritoneal macrophages as a method to reduce both local and systemic inflammation, thereby presenting a novel strategy for arthritis treatment.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.