Amphiphilic Phosphorus Dendrons Associated with Anti-inflammatory siRNA Reduce Symptoms in Murine Collagen-Induced Arthritis.

Abstract

Small interfering RNA (siRNA) holds promise for treating rheumatoid arthritis by inhibiting major cytokines such as tumor necrosis factor-α (TNF-α). We developed original cationic amphiphilic phosphorus dendrons to produce dendriplexes associated with TNF-α siRNA. The dendrons were made of 10 pyrrolidinium end groups and a C17 aliphatic chain. The dendriplexes demonstrated the ability to protect siRNA from nuclease degradation and to promote macrophage uptake. Moreover, they led to potent inhibition of TNF-α expression in the lipopolysaccharide-activated mouse macrophage cell line RAW264.7 in vitro model. A significant anti-inflammatory effect in the murine collagen-induced arthritis model was observed through arthritis scoring and histological observations. These results open up essential perspectives in using this original amphiphilic dendron to reduce the disease burden and improve outcomes in chronic inflammatory diseases.

• Authors: Zhibo Yu, Nicolas Tsapis, François Fay, Liang Chen, Andrii Karpus, Xiangyang Shi, Catherine Cailleau, Samuel García Pérez, Nicolas Huang, Juliette Vergnaud, Serge Mignani, Jean-Pierre Majoral, Elias Fattal
• Journal: Biomacromolecules (Biomacromolecules) Vol. 24 Issue 2 Pg. 667-677 (02 13 2023) ISSN: 1526-4602 [Electronic] United States
• PMID: 36599673 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Small Interfering
• Tumor Necrosis Factor-alpha
• Dendrimers
• Anti-Inflammatory Agents

Topics

• Animals
• Mice
• Arthritis, Experimental (drug therapy, genetics)
• RNA, Small Interfering (genetics, pharmacology)
• Tumor Necrosis Factor-alpha (genetics)
• Dendrimers
• Anti-Inflammatory Agents (pharmacology)