Reprogramming Lesional Macrophage Homeostasis via Interferon Regulatory Factor 5 Targeted siRNA Nanoimmunotherapy for Atherosclerosis - PubMed
12 hours ago
- #nanoimmunotherapy
- #macrophage
- #atherosclerosis
- Atherosclerotic macrophages show a pro-inflammatory phenotype, accelerating disease progression.
- Interferon regulatory factor 5 (IRF5) is highly expressed in lesional macrophages and promotes pro-inflammatory cytokine secretion.
- Current therapies lack effective strategies to specifically silence IRF5 in lesional macrophages.
- A dual-targeted siRNA-based nanotherapeutic platform was developed to selectively target IRF5 in plaque macrophages.
- The platform uses liposome-based nano-immunotherapeutics encapsulating siRNA against IRF5 (siIRF5).
- In mouse models, the therapy effectively accumulated in lesional macrophages, downregulated IRF5, and promoted anti-inflammatory macrophage polarization.
- The treatment reduced plaque burden and enhanced plaque stability in two independent murine models.
- The siIRF5 nanoimmunotherapy showed biocompatibility even after long-term administration, indicating clinical potential.
- This strategy offers a promising therapeutic avenue for atherosclerosis and other macrophage-driven inflammatory diseases.