期刊
ACTA BIOMATERIALIA
卷 6, 期 10, 页码 3927-3935出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.actbio.2010.04.021
关键词
Liver targeting; Glycyrrhetinic acid; Block co-polymers; Micelles; Doxorubicin
资金
- National Natural Science Foundation of China [50873048]
- State Key Fundamental RD Project [2005CB623904]
- State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences [2005CB623904]
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 (IC50 47 ng ml(-1)) was much higher than that of free DOX (IC50 90 ng ml(-1)) These results indicate that GA-modified micelles have great potential in liver targeting therapy (C) 2010 Acta Materialia Inc Published by Elsevier Ltd. All rights reserved.
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