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Dual-modified cationic liposomes loaded with paclitaxel and survivin siRNA for targeted imaging and therapy of cancer stem cells in brain glioma.
Drug Delivery ( IF 6.5 ) Pub Date : 2018-10-03 , DOI: 10.1080/10717544.2018.1494225
Xiyang Sun 1 , Ying Chen 1 , Hui Zhao 2 , Guanglei Qiao 1 , Meiyang Liu 3 , Chunlei Zhang 3 , Daxiang Cui 3, 4 , Lijun Ma 1
Affiliation  

Development of safe, efficient nanocomplex for targeted imaging and therapy of cancer stem cells in brain glioma has become a great challenge. Herein, a low-density lipoprotein receptor-related protein and a RNA aptamer bound CD133 were used as dual-targeting ligands to prepare dual-modified cationic liposomes (DP-CLPs) loaded with survivin siRNA and paclitaxel (DP-CLPs-PTX-siRNA) for actively targeting imaging and treating CD133+ glioma stem cells after passing through the blood-brain barrier. After being administrated with DP-CLPs-PTX-siRNA nanocomplex, DP-CLPs showed a persistent target ability to bind glioma cells and brain microvascular endothelial cells (BCECs) and to deliver drugs (PTX/siRNA) to CD133+ glioma stem cells. Prepared DP-CLPs-PTX-siRNA nanocomplex showed very low cytotoxicity to BCECs, but induced selectively apoptosis of CD133+ glioma stem cells, and improved CD133+ glioma stem cells' differentiation into non-stem-cell lineages, also markedly inhibited tumorigenesis, induced CD133+ glioma cell apoptosis in intracranial glioma tumor-bearing nude mice and improved survival rates. In conclusion, prepared DP-CLPs-PTX-siRNA nanocomplex selectively induced CD133+ glioma stem cell apoptosis in vitro and in vivo exhibits great potential for targeted imaging and therapy of brain glioma stem cells.

中文翻译:

载有紫杉醇和survivin siRNA的双修饰阳离子脂质体,用于脑胶质瘤中癌症干细胞的靶向成像和治疗。

开发用于脑胶质瘤中癌症干细胞靶向成像和治疗的安全,有效的纳米复合物已成为一项巨大的挑战。在本文中,低密度脂蛋白受体相关蛋白和RNA适体结合的CD133被用作双重靶向配体,以制备载有survivin siRNA和紫杉醇(DP-CLPs-PTX-siRNA)的双重修饰阳离子脂质体(DP-CLP)。 ),用于在穿过血脑屏障后主动靶向成像并治疗CD133 +胶质瘤干细胞。在用DP-CLPs-PTX-siRNA纳米复合物给药后,DP-CLPs具有结合胶质瘤细胞和脑微血管内皮细胞(BCEC)以及向CD133 +胶质瘤干细胞递送药物(PTX / siRNA)的持久目标能力。制备的DP-CLPs-PTX-siRNA纳米复合物对BCEC的细胞毒性非常低,但可选择性诱导CD133 +胶质瘤干细胞凋亡,并改善CD133 +胶质瘤干细胞向非干细胞谱系的分化,还显着抑制肿瘤发生,诱导颅内神经胶质瘤荷瘤裸鼠CD133 +胶质瘤细胞凋亡并提高存活率。总之,制备的DP-CLPs-PTX-siRNA纳米复合物在体外和体内选择性诱导CD133 +神经胶质瘤干细胞凋亡,具有针对脑胶质瘤干细胞的靶向成像和治疗的巨大潜力。
更新日期:2018-10-01
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