Amphiphilic Phosphorus Dendrons Associated with Anti-inflammatory siRNA Reduce Symptoms in Murine Collagen-Induced Arthritis.
Zhibo YuNicolas TsapisFrançois FayLiang ChenAndrii KarpusXiangyang ShiCatherine CailleauSamuel García PérezNicolas HuangJuliette VergnaudSerge MignaniJean-Pierre MajoralElias FattalPublished in: Biomacromolecules (2023)
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.
Keyphrases
- rheumatoid arthritis
- anti inflammatory
- disease activity
- cancer therapy
- high glucose
- interstitial lung disease
- ankylosing spondylitis
- diabetic rats
- drug induced
- poor prognosis
- adipose tissue
- oxidative stress
- hyaluronic acid
- inflammatory response
- minimally invasive
- signaling pathway
- endothelial cells
- depressive symptoms
- sewage sludge
- risk factors
- deep learning
- sleep quality
- skeletal muscle
- tissue engineering
- transcription factor
- immune response
- insulin resistance
- heavy metals