在脂质纳米颗粒中掺入甘草酸和多烯磷脂酰胆碱可通过传递p65 siRNA改善急性肝损伤。

IF 4.2 2区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Nanomedicine : nanotechnology, biology, and medicine Pub Date : 2022-12-01 DOI:10.2139/ssrn.4096906

Qiming Yin, Xiangling Song, Peng-fei Yang, Wen Yang, Xinyu Li, Xuejun Wang, Shengnan Wang

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引用次数: 3

摘要

肝炎引起的肝损伤是多种肝脏疾病的病理基础，具有较高的发病率和死亡率。尽管siRNA在肝炎治疗中似乎很有前景，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，降低细胞毒性并提高siRNA的稳定性。通过肝脏组织学、血液学和促炎细胞因子分析评估，GA/ ppc修饰的LNP和siRNA脂质复合物靶向NF-κB(炎症的关键介质)，减轻急性肝损伤。此外，GA/ ppc修饰的LNPs可以有效地在细胞内传递反义寡核苷酸(ASOs)和mRNA，抑制病毒感染。综上所述，GA/ ppc修饰的LNPs可以作为一种有前景的核酸治疗递送系统。

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Incorporation of glycyrrhizic acid and polyene phosphatidylcholine in lipid nanoparticles ameliorates acute liver injury via delivering p65 siRNA.

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.

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来源期刊

Nanomedicine : nanotechnology, biology, and medicine 工程技术-纳米科技

CiteScore

11.10

自引率

0.00%

发文量

133

审稿时长

42 days

期刊介绍： The mission of Nanomedicine: Nanotechnology, Biology, and Medicine (Nanomedicine: NBM) is to promote the emerging interdisciplinary field of nanomedicine. Nanomedicine: NBM is an international, peer-reviewed journal presenting novel, significant, and interdisciplinary theoretical and experimental results related to nanoscience and nanotechnology in the life and health sciences. Content includes basic, translational, and clinical research addressing diagnosis, treatment, monitoring, prediction, and prevention of diseases.