Dual-modified cationic liposomes loaded with paclitaxel and survivin siRNA for targeted imaging and therapy of cancer stem cells in brain glioma

Drug Delivery

Guanglei Qiao¹  Lijun Ma¹  Xiyang Sun¹  Hui Zhao¹  Ying Chen¹  Chunlei Zhang²  Meiyang Liu²  Daxiang Cui² 

[1] Shanghai Jiao Tong University School of Medicine;Shanghai Jiao Tong University;

关键词: glioma stem cells;    survivin sirna;    paclitaxel;    targeted imaging;    targeted therapy;   

DOI  :  10.1080/10717544.2018.1494225

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown