Journal
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
Volume 48, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.nano.2022.102649
Keywords
Lipid nanoparticle; Glycyrrhizic acid; Inflammation; Acute liver injury
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In this study, a new strategy of incorporating glycyrrhizic acid (GA) and polyene phosphatidylcholine (PPC) into lipid nanoparticles (GA/PPC-modified LNPs) was developed, which showed enhanced cellular uptake, improved gene-silencing efficiency, reduced cytotoxicity, and increased siRNA stability. GA/PPC-modified LNPs targeting NF-kappa B attenuated acute liver injury and facilitated intracellular delivery of antisense oligonucleotides (ASOs) and mRNA inhibiting viral infection. These findings suggest that GA/PPC-modified LNPs could serve as a promising nucleic acid delivery system.
Liver injury caused by hepatitis is the pathological basis of varied hepatic diseases with high morbidity and mortality. Although siRNA appears promising in therapeutics of hepatitis, efficient and safe delivery remains a challenge. In this study, we developed a new strategy of incorporating glycyrrhizic acid (GA) and polyene phosphatidylcholine (PPC) into lipid nanoparticles (GA/PPC-modified LNPs), which was capable of promoting cellular uptake, enhancing gene-silencing, reducing cytotoxicity and improving siRNA stability. GA/PPC-modified LNP and siRNA lipoplex targeting NF-kappa B, a key mediator of inflammation, mitigates acute liver injury, as assessed by liver histology, hematological and pro-inflammatory cytokine analysis. Furthermore, GA/PPC-modified LNPs reveal efficiently intracellular delivery of antisense oligonucleotides (ASOs) and mRNA inhibiting viral infection. In conclusion, GA/PPC-modified LNPs could be used as a promising delivery system for nucleic acid-based therapy. (c) 2022 Elsevier Inc. All rights reserved.
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