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

Drug Delivery

Hui Zhao¹  Guanglei Qiao²  Lijun Ma²  Xiyang Sun²  Ying Chen²  Chunlei Zhang³  Meiyang Liu³  Daxiang Cui⁴ 

[1] Department of Geriatrics, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China;Department of Oncology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China;Institute of Nano Biomedicine and Engineering, Shanghai Engineering Research Center for Intelligent Instrument for Diagnosis and Therapy, Department of Instrument Science and Engineering, Shanghai Jiao Tong University, Shanghai, PR China;Institute of Nano Biomedicine and Engineering, Shanghai Engineering Research Center for Intelligent Instrument for Diagnosis and Therapy, Department of Instrument Science and Engineering, Shanghai Jiao Tong University, Shanghai, PR China;National Center for Translational Medicine, Collaborative Innovational Center for System Biology, Shanghai Jiao Tong University, Shanghai, PR Chin;

关键词: Glioma stem cells;    survivin siRNA;    paclitaxel;    targeted imaging;    targeted therapy;   

DOI  :  10.1080/10717544.2018.1494225

来源: publisher

【 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】

CC BY