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首页> 外文期刊>Acta biomaterialia >Glycyrrhetinic acid-modified poly(ethylene glycol)-b-poly(gamma-benzyl l-glutamate) micelles for liver targeting therapy.
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Glycyrrhetinic acid-modified poly(ethylene glycol)-b-poly(gamma-benzyl l-glutamate) micelles for liver targeting therapy.

机译：甘草次酸修饰的聚（乙二醇）-b-聚（γ-苄基-1-谷氨酸）胶束用于肝靶向治疗。

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摘要

Liver targeted micelles were successfully constructed via self-assembly of glycyrrhetinic acid (GA)-modified poly(ethylene glycol)-b-poly(gamma-benzyl l-glutamate) (GA-PEG-PBLG) block co-polymers, which were fabricated via ring opening polymerization of gamma-benzyl l-glutamate N-carboxyanhydride monomer initiated by GA-modified PEG. The in vivo biodistribution and the in vitro cellular uptake of these micelles were investigated. The results showed that the relative uptake of doxorubicin (DOX)-loaded micelles (DOX/GA-PEG-PBLG) in liver was much higher than in other tissues, and the resulting DOX concentration in liver was about 2.2-fold higher than that from the micelles without modification by GA. Moreover, the cellular uptake study demonstrated that the introduction of GA to the micelles could significantly increase the affinity for human hepatic carcinoma 7703 cells, which induced a 3.7-fold higher endocytosis than unmodified ones. The cytotoxicity of DOX/GA-PEG-PBLG micelles (IC(50) 47 ngml(-1)) was much higher than that of free DOX (IC(50) 90 ngml(-1)). These results indicate that GA-modified micelles have great potential in liver targeting therapy.
机译：通过甘草次酸（GA）改性的聚（乙二醇）-b-聚（γ-苄基-1-谷氨酸）（GA-PEG-PBLG）嵌段共聚物的自组装成功构建了肝靶向胶束通过GA修饰的PEG引发的γ-苄基1-谷氨酸N-羧基酐单体的开环聚合反应。研究了这些胶束的体内生物分布和体外细胞摄取。结果表明，阿霉素（DOX）负载的胶束（DOX / GA-PEG-PBLG）在肝脏中的相对摄取远高于其他组织，并且肝脏中产生的DOX浓度比从组织中摄取的高约2.2倍。未经GA修饰的胶束。此外，细胞摄取研究表明，向胶束中引入GA可以显着提高对人肝癌7703细胞的亲和力，与未修饰的细胞相比，其诱导的内吞作用高3.7倍。 DOX / GA-PEG-PBLG胶束（IC（50）47 ngml（-1））的细胞毒性远高于游离DOX（IC（50）90 ngml（-1））的细胞毒性。这些结果表明，GA修饰的胶束在肝靶向治疗中具有巨大的潜力。

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