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 re-mains 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 re-port a mannose-modified LNP(M-MC3 LNP@TNFα)loading tumor necrosis factor α(TNFα)siRNA for tar-geting 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.
维普
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