Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, PR China.
Biomaterials. 2013 Jul;34(22):5628-39. doi: 10.1016/j.biomaterials.2013.03.097. Epub 2013 Apr 26.
Effective chemotherapy for glioblastoma requires a carrier that can penetrate the blood-brain barrier (BBB) and subsequently target the glioma cells. Dual-targeting doxorubincin (Dox) liposomes were produced by conjugating liposomes with both folate (F) and transferrin (Tf), which were proven effective in penetrating the BBB and targeting tumors, respectively. The liposome was characterized by particle size, Dox entrapment efficiency, and in vitro release profile. Drug accumulation in cells, P-glycoprotein (P-gp) expression, and drug transport across the BBB in the dual-targeting liposome group were examined by using bEnd3 BBB models. In vivo studies demonstrated that the dual-targeting Dox liposomes could transport across the BBB and mainly distribute in the brain glioma. The anti-tumor effect of the dual-targeting liposome was also demonstrated by the increased survival time, decreased tumor volume, and results of both hematoxylin-eosin staining and terminal deoxynucleotidyl transferase dUTP nick end labeling analysis. The dual-targeting Dox liposome could improve the therapeutic efficacy of brain glioma and were less toxic than the Dox solution, showing a dual-targeting effect. These results indicate that this dual-targeting liposome can be used as a potential carrier for glioma chemotherapy.
有效的脑胶质瘤化疗需要一种既能穿透血脑屏障（BBB）又能靶向脑胶质瘤细胞的载体。通过将脂质体与叶酸（F）和转铁蛋白（Tf）连接，制备了双重靶向阿霉素脂质体，这两种物质分别被证明能有效穿透 BBB 和靶向肿瘤。通过测定粒径、阿霉素包封率和体外释放曲线对脂质体进行了表征。利用 bEnd3BBB 模型检测了细胞内药物蓄积、P-糖蛋白（P-gp）表达和药物在双重靶向脂质体组中的跨 BBB 转运情况。体内研究表明，双重靶向阿霉素脂质体能够穿透 BBB 并主要分布于脑胶质瘤中。双重靶向脂质体还通过延长生存时间、减小肿瘤体积以及苏木精-伊红染色和末端脱氧核苷酸转移酶 dUTP 缺口末端标记分析的结果，证明了其对肿瘤的治疗效果。与阿霉素溶液相比，双重靶向阿霉素脂质体的毒性更低，治疗效果更好，显示出双重靶向作用。这些结果表明，该双重靶向脂质体可用作脑胶质瘤化疗的潜在载体。
