Hepatic stellate cells (HSCs) were activated and secreted excessive amounts of extracellular matrix (ECM) proteins during pathogenetic progress of liver fibrosis. Germacrone (GMO) and miR-29b can play an important role in inhibiting growth of HSCs and production of type I collagen. GMO and miR-29b were co-encapsulated into nanoparticles (NPs) based on poly(ethylene glycol)-block-poly(lactide-co-glycolide) (PEG-PLGA). Then, NPs were modified with cyclic RGD peptides (cRGDfK). cRGDfK is an effective ligand to bind integrin αvβ3 and increase the targeting ability for fibrotic liver. GMO- and miR-29b-loaded NPs exhibited great cytotoxicity to activated HSCs and significantly inhibited production of type I collagen. Liver fibrosis model of mice was induced by administration of carbon tetrachloride. Great targeting ability was achieved in liver fibrotic mice treated with cRGD-modified NPs. Significant ant-fibrotic effects have been presented based on hematoxylin and eosin (H&E), Masson and Sirius Red staining results of liver tissues collected from mice treated with drug-loaded NPs. All these results indicate GMO- and miR-29b-loaded cRGD-modified NPs have the potential for clinical use to treat liver fibrosis.

中文翻译：

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基于环状RGD修饰的纳米颗粒的miR-29b和杀菌龙的共同交付，用于肝纤维化治疗。

在肝纤维化的致病过程中，肝星状细胞（HSC）被激活并分泌过量的细胞外基质（ECM）蛋白。Germacrone（GMO）和miR-29b在抑制HSC的生长和I型胶原的产生中起重要作用。将GMO和miR-29b共封装到基于聚（乙二醇）-嵌段-聚（丙交酯-共-乙交酯）（PEG-PLGA）的纳米粒子（NPs）中。然后，用环状RGD肽（cRGDfK）修饰NP。cRGDfK是结合整联蛋白αvβ3并增加对纤维化肝的靶向能力的有效配体。载有GMO和miR-29b的NP对活化的HSC表现出极大的细胞毒性，并显着抑制I型胶原蛋白的产生。通过施用四氯化碳诱导小鼠肝纤维化模型。在用cRGD修饰的NPs治疗的肝纤维化小鼠中实现了出色的靶向能力。基于苏木精和曙红（H＆E），从用载药的NPs处理的小鼠收集的肝脏组织的Masson和Sirius Red染色结果，已显示出明显的抗纤维化作用。所有这些结果表明，载有GMO和miR-29b的cRGD修饰的NP具有临床应用治疗肝纤维化的潜力。