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• W4313377529 endingPage "122489" @default.
• W4313377529 startingPage "122489" @default.
• W4313377529 abstract "Small interfering RNA (siRNA) mediating specific gene silencing provides a promising strategy for anti-inflammatory therapy. However, the development of potent carriers for anti-inflammatory siRNA to macrophages remains challenging. With the aim of realizing potent delivery of siRNA to macrophages, we engineered ionizable lipid nanoparticles (LNPs) with the key component of synthetic lipid-like materials. By varying the amine molecules in the structure of synthetic lipid-like materials, a potent LNP (1O14-LNP) was identified, which exhibited efficient transfection of macrophages by facilitating efficient internalization and endosomal escape. The 1O14-LNP successfully delivered anti-inflammatory siRNA against interleukin-1β (siIL-1β) with more than 90% downregulation of IL-1β expression in LPS-activated macrophages. From in vivo studies, systemic administrated 1O14-LNP/siRNA mainly distributed in liver and efficiently captured by hepatic macrophages without notable sign of toxicity. Furthermore, LPS/d-GalN-induced acute liver injury model treated with 1O14-LNP/siIL-1β resulted in significant suppression of IL-1β expression and amelioration of liver tissue damage. These results demonstrate that the engineered ionizable LNP provides a powerful tool for siRNA delivery to macrophages and that the strategy of silencing of pro-inflammatory cytokines holds great potential for treating inflammatory diseases." @default.
• W4313377529 created "2023-01-06" @default.
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• W4313377529 date "2023-01-01" @default.
• W4313377529 modified "2023-09-27" @default.
• W4313377529 title "Engineered ionizable lipid nanoparticles mediated efficient siRNA delivery to macrophages for anti-inflammatory treatment of acute liver injury" @default.
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• W4313377529 doi "https://doi.org/10.1016/j.ijpharm.2022.122489" @default.
• W4313377529 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36521639" @default.
• W4313377529 hasPublicationYear "2023" @default.
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