Citation: Qiu Wang, Qikun Jiang, Dan Li, Zimeng Yang, Lin Gao, Fan Liu, Chang Li, Yao Feng, Zhonggui He, Cong Luo, Jin Sun. Elaborately engineering of lipid nanoparticle for targeting delivery of siRNA and suppressing acute liver injury[J]. Chinese Chemical Letters, ;2024, 35(2): 108683. doi: 10.1016/j.cclet.2023.108683 shu

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

Qiu Wang ^{a, 1} ,
Qikun Jiang ^{a, 1} ,
Dan Li ^a ,
Zimeng Yang ^a ,
Lin Gao ^a ,
Fan Liu ^a ,
Chang Li ^a ,
Yao Feng ^b ,
Zhonggui He ^a ,
Cong Luo ^{a, *,} ,
Jin Sun ^{a, *,}

a.
Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China
b.
Kangya of Ningxia Pharmaceutical Co. Ltd., Yinchuan 750000, China

luocong@syphu.edu.cn

sunjin@syphu.edu.cn

Received Date: 2 March 2023
Revised Date: 7 June 2023
Accepted Date: 11 June 2023
Available Online: 17 June 2023

Figures(6)

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.
- Lipid nanoparticle,
- Targeting siRNA delivery,
- Acute liver injury,
- Gene silencing,
- Tumor necrosis factor α
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