Elaborately engineering of lipid nanoparticle for targeting delivery of siRNA and suppressing acute liver injury

IF 8.9 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Chinese Chemical Letters Pub Date : 2023-06-17 DOI:10.1016/j.cclet.2023.108683

Qiu Wang , Qikun Jiang , Dan Li , Zimeng Yang , Lin Gao , Fan Liu , Chang Li , Yao Feng , Zhonggui He , Cong Luo , Jin Sun

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引用次数: 1

Abstract

Small interfering RNA (siRNA)-based gene silencing has been considered as a potential therapy modality against inflammatory diseases. Nevertheless, the effective delivery of siRNA to desired destination still remains challenging due to poor stability, high molecular weight and negative charge. Currently, ionizable lipid nanoparticle (LNP) has been extensively used as vector for effective delivery of siRNA. Herein, we report a mannose-modified LNP (M-MC3 LNP@TNFα) loading tumor necrosis factor α (TNFα) siRNA for targeting liver macrophages, achieving effectively inhibit acute liver injury. The M-MC3 LNP@TNFα not only increases the internalization of LNP by macrophages, but also enhances the gene silencing efficiency of TNFα in vitro. Additionally, the M-MC3 LNP@TNFα exhibits higher accumulation in liver of healthy mice than that of MC3 LNP@TNFα (un-modified LNP) owing to the targeting effect of mannose. As expected, the M-MC3 LNP@TNFα significantly suppresses the expression of TNFα and ameliorates liver damage in acute liver injury model. Such a LNP targeting siRNA delivery holds great potential for the treatment of diseases associated with liver in the future.

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精心设计的靶向siRNA递送和抑制急性肝损伤的脂质纳米颗粒

基于小干扰RNA (siRNA)的基因沉默被认为是一种潜在的治疗炎症性疾病的方法。然而，由于稳定性差、分子量高和负电荷，siRNA的有效递送仍然具有挑战性。目前，可电离脂质纳米颗粒(LNP)已被广泛用作siRNA的有效递送载体。本文报道了一种甘露糖修饰的LNP (M-MC3 LNP@TNFα)装载肿瘤坏死因子α (TNFα) siRNA靶向肝巨噬细胞，有效抑制急性肝损伤。M-MC3 LNP@TNFα不仅能增加巨噬细胞对LNP的内化，还能提高TNFα在体外的基因沉默效率。此外，由于甘露糖的靶向作用，M-MC3 LNP@TNFα在健康小鼠肝脏中的积累量高于MC3 LNP@TNFα(未修饰LNP)。正如预期的那样，M-MC3 LNP@TNFα在急性肝损伤模型中显著抑制TNFα的表达，改善肝损伤。这种靶向siRNA递送的LNP在未来治疗肝脏相关疾病方面具有很大的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Chinese Chemical Letters 化学-化学综合

CiteScore

14.10

自引率

15.40%

发文量

8969

审稿时长

1.6 months

期刊介绍： Chinese Chemical Letters (CCL) (ISSN 1001-8417) was founded in July 1990. The journal publishes preliminary accounts in the whole field of chemistry, including inorganic chemistry, organic chemistry, analytical chemistry, physical chemistry, polymer chemistry, applied chemistry, etc.Chinese Chemical Letters does not accept articles previously published or scheduled to be published. To verify originality, your article may be checked by the originality detection service CrossCheck.