靶向肿瘤新生血管的阿霉素脂质体的体内药效学研究

靶向肿瘤新生血管的阿霉素脂质体的体内药效学研究

庄崧, 齐宪荣^*

北京大学药学院药剂教研室, 北京 100191

收稿日期:2009-04-29 修回日期:2009-08-10 出版日期:2009-09-15 发布日期:2009-09-15
通讯作者: 齐宪荣*

Antitumor efficacy of doxorubicin encapsulated in neovasculature targeting liposomes

Song Zhuang, Xian-Rong Qi^*

Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China

Received:2009-04-29 Revised:2009-08-10 Online:2009-09-15 Published:2009-09-15
Contact: Xian-Rong Qi*

摘要/Abstract

摘要：

抗新生血管治疗是一种很有效的抗血管新生化疗方法, 它通过将细胞毒药物运送到新生血管内皮细胞从而破坏新形成的血管, 达到间接消灭肿瘤细胞的目的。近来有报道表明, APRPG五肽可以特异性地与肿瘤新生血管结合。我们使用APRPG与二硬脂酰磷脂酰乙醇胺的共聚物 (DSPE-PEG-APRPG) 来修饰脂质体, 探讨包载多柔比星的新生血管靶向的脂质体 (APRPG-LP) 对Lewis肺癌 (LLC) 肿瘤的抗肿瘤效果。结果表明, APRPG修饰的多柔比星脂质体相比于普通的多柔比星脂质体 (LP), 游离多柔比星溶液 (Free DOX) 和生理盐水 (Saline), 既显著地抑制了肿瘤的生长 (P<0.001), 又显著地延长了荷瘤小鼠的生存时间 (P<0.01), 这是由于APRPG-LP可以破坏肿瘤新生血管, 更加有效地杀死肿瘤细胞。因此, APRPG-LP是一种较好的能将药物靶向输送到肿瘤新生血管部位的药物载体。

关键词: 脂质体, 多柔比星, 抗肿瘤效果, 血管新生, 主动靶向

Abstract: It was reported that a 5-amino acid peptide Ala-Pro-Arg-Pro-Gly (APRPG) could specifically bind to the tumor angiogenic site. We investigated the antitumor efficacy of doxorubicin (DOX) encapsulated in APRPG modified liposome (APRPG-LP) compared with DOX encapsulated in non-APRPG modified liposomes (LP) and DOX solution (free DOX) on Lewis lung carcinoma (LLC) bearing mice. APRPG-LP could efficiently suppress the tumor growth of the experimental mice, compared with LP (P<0.001), free DOX (P<0.001) and saline of negative control (P<0.001). The present results demonstrated that the APRPG modified liposomes exhibited a much better therapeutic efficacy over the non-modified liposomes and the DOX solution, because of the effect of targeted tumor angiogenesis disruption. Thus, APRPG-LP could be a promising active-targeting drug carrier to tumor angiogenic site.

Key words: Liposomes, Liposomes, Doxorubicin, Doxorubicin, Antitumor efficacy, Antitumor efficacy, Angiogenesis, Angiogenesis, Active targeting, Active targeting

中图分类号:

R943.42

Supporting:

Foundation items: National Natural Science Foundation of China (Grant No. 30772665), Beijing Nature Science Foundation (Grant No. 7083111).
^*Corresponding author. Tel./fax: 86-10-82801584; e-mail: qixr@bjmu.edu.cn

庄崧, 齐宪荣^*. 靶向肿瘤新生血管的阿霉素脂质体的体内药效学研究[J]. .

Song Zhuang, Xian-Rong Qi^*. Antitumor efficacy of doxorubicin encapsulated in neovasculature targeting liposomes [J]. .

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