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

Xiyang Sun; Ying Chen; Hui Zhao; Guanglei Qiao; Meiyang Liu; Chunlei Zhang; Daxiang Cui; Lijun Ma

doi:10.1080/10717544.2018.1494225

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

Drug Deliv. 2018 Nov;25(1):1718-1727. doi: 10.1080/10717544.2018.1494225.

Authors

Xiyang Sun¹, Ying Chen¹, Hui Zhao², Guanglei Qiao¹, Meiyang Liu³, Chunlei Zhang³, Daxiang Cui^{3

4}, Lijun Ma¹

Affiliations

¹ a Department of Oncology, Tongren Hospital , Shanghai Jiao Tong University School of Medicine , Shanghai , PR China.
² b Department of Geriatrics, Tongren Hospital , Shanghai Jiao Tong University School of Medicine , Shanghai , PR China.
³ c 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.
⁴ d National Center for Translational Medicine, Collaborative Innovational Center for System Biology , Shanghai Jiao Tong University , Shanghai , PR China.

Abstract

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.

Keywords: Glioma stem cells; paclitaxel; survivin siRNA; targeted imaging; targeted therapy.

MeSH terms

Animals
Antineoplastic Agents / administration & dosage*
Brain Neoplasms* / diagnostic imaging
Brain Neoplasms* / pathology
Brain Neoplasms* / therapy
Cell Line, Tumor
Glioma* / diagnostic imaging
Glioma* / pathology
Glioma* / therapy
Humans
Liposomes* / chemistry
Male
Mice
Mice, Inbred BALB C
Neoplastic Stem Cells / drug effects
Paclitaxel / administration & dosage*
RNA, Small Interfering / administration & dosage*
RNA, Small Interfering / genetics
Survivin / genetics

Substances

Antineoplastic Agents
Liposomes
RNA, Small Interfering
Survivin
Paclitaxel

Grants and funding

This work was supported by the National Key Basic Research Program (project no 2017FYA0205300), National Natural Science Foundation of China (no 81602184), Foundation of Tongren Hospital, Shanghai Jiao Tong University, School of Medicine (no TRYJ201515) and Medical engineering cross project of Shanghai Jiao Tong University (no YG2016ZD10).