State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, AMMS, Beijing 100071, People's Republic of China; School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, People's Republic of China.
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, AMMS, Beijing 100071, People's Republic of China.
Nanomedicine. 2023 Feb;48:102649. doi: 10.1016/j.nano.2022.102649. Epub 2022 Dec 27.
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发病率和死亡率高的多种肝脏疾病的病理基础。尽管 siRNA 在肝炎治疗中具有广阔的应用前景，但高效、安全的递送仍然是一个挑战。在本研究中，我们开发了一种将甘草酸（GA）和多烯磷脂酰胆碱（PPC）整合到脂质纳米颗粒（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 稳定性。靶向 NF-κB（炎症的关键介质）的 GA/PPC 修饰的 LNP 和 siRNA 脂质体通过肝组织学、血液学和促炎细胞因子分析减轻急性肝损伤。此外，GA/PPC 修饰的 LNPs 可有效递送至细胞内的反义寡核苷酸（ASOs）和 mRNA，抑制病毒感染。总之，GA/PPC 修饰的 LNPs 可用作基于核酸的治疗的有前途的递送系统。
