Enhanced Intracellular Delivery and Chemotherapy for Glioma Rats by Transferrin-Conjugated Biodegradable Polymersomes Loaded with Doxorubicin

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• 作者：Zhiqing Pang ; Huile Gao ; Yuan Yu ; Liangran Guo ; Jun Chen ; Shuaiqi Pan ; Jinfeng Ren ; Ziyi Wen ; Xinguo Jiang
• 刊名：Bioconjugate Chemistry
• 出版年：2011
• 出版时间：June 15, 2011
• 年：2011
• 卷：22
• 期：6
• 页码：1171-1180
• 全文大小：1002K
• 年卷期：v.22,no.6(June 15, 2011)
• ISSN：1520-4812

文摘

A brain drug delivery system for glioma chemotherapy based on transferrin-conjugated biodegradable polymersomes, Tf-PO鈭扗OX, was made and evaluated with doxorubicin (DOX) as a model drug. Biodegradable polymersomes (PO) loaded with doxorubicin (DOX) were prepared by the nanoprecipitation method (PO鈭扗OX) and then conjugated with transferrin (Tf) to yield Tf-PO鈭扗OX with an average diameter of 107 nm and surface Tf molecule number per polymersome of approximately 35. Compared with PO鈭扗OX and free DOX, Tf-PO鈭扗OX demonstrated the strongest cytotoxicity against C6 glioma cells and the greatest intracellular delivery. It was shown in pharmacokinetic and brain distribution experiments that Tf-PO significantly enhanced brain delivery of DOX, especially the delivery of DOX into brain tumor cells. Pharmacodynamics results revealed a significant reduction of tumor volume and a significant increase of median survival time in the group of Tf-PO鈭扗OX compared with those in saline control animals, animals treated with PO鈭扗OX, and free DOX solution. By terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling, Tf-PO鈭扗OX could extensively make tumor cell apoptosis. These results indicated that Tf-PO鈭扗OX could significantly enhance the intracellular delivery of DOX in glioma and the chemotherapeutic effect of DOX for glioma rats.