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：

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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。