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-κB, 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.

肝炎引起的肝损伤是多种肝病的病理基础，具有很高的发病率和死亡率。尽管 siRNA 在肝炎治疗中看起来很有前途，但有效和安全的递送仍然是一个挑战。在这项研究中，我们开发了一种将甘草酸 (GA) 和多烯磷脂酰胆碱 (PPC) 结合到脂质纳米粒子（GA/PPC 修饰的 LNPs）中的新策略，该策略能够促进细胞摄取、增强基因沉默、降低细胞毒性和提高 siRNA 的稳定性。GA/PPC 修饰的 LNP 和 siRNA 脂质复合物靶向炎症的关键介质 NF-κB，可减轻急性肝损伤，通过肝脏组织学、血液学和促炎细胞因子分析进行评估。此外，GA/PPC 修饰的 LNP 揭示了反义寡核苷酸 (ASO) 和 mRNA 抑制病毒感染的有效细胞内递送。总之，GA/PPC 修饰的 LNP 可用作基于核酸的治疗的有前途的递送系统。