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Simultaneous elimination of cancer stem cells and bulk cancer cells by cationic-lipid-assisted nanoparticles for cancer therapy

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Abstract

Convincing evidence indicates that the existence of cancer stem cells (CSCs) within malignant tumors is mostly responsible for the failure of chemotherapy. Therefore, instead of merely targeting bulk cancer cells, simultaneous elimination of both CSCs and bulk cancer cells is necessary to improve therapeutic outcomes. Herein, we designed cationic-lipid-assisted nanoparticles DTXLNPsiRNA for simultaneous encapsulation of the conventional chemotherapeutic agentdocetaxel (DTXL) and small interfering RNA (siRNA) targeting BMI-1 (siBMI-1). We confirmed that nanoparticles DTXLNPsiBMI-1 effectively deliver both therapeutic agents into CSCs and bulk cancer cells. The bulk cancer cells were effectively killed by the DTXL encapsulated in DTXLNPsiBMI-1. In breast CSCs, BMI-1 expression was significantly downregulated by DTXLNPsiBMI-1; consequently, the stemness was reduced and chemosensitivity of CSCs to DTXL was enhanced, resulting in the elimination of CSCs. Therefore, via DTXLNPsiBMI-1, the combination of siBMI-1 and DTXL completely inhibited tumor growth and prevented a relapse by synergistic killing of CSCs and bulk cancer cells in a murine model of an MDA-MB-231 orthotropic tumor.

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Acknowledgements

This work was partially supported by the National Key R&D Program of China (No. 2017YFA0205600), the National Basic Research Program of China (No. 2015CB932100), the National Natural Science Foundation of China (Nos. 51390482, 51633008, and 31470965), National Postdoctoral Program for Innovative Talents (No. BX201700080) and China Postdoctoral Science Foundation (No. 2017M622676).

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  1. Kaige Chen and Song Shen contributed equally to this work.

Authors and Affiliations

  1. School of Life Sciences, University of Science and Technology of China, Hefei, 230027, China

    Kaige Chen, Gui Zhao & Jun Wang

  2. Institutes for Life Sciences, and School of Medicine, South China University of Technology, Guangzhou, 510006, China

    Song Shen, Xianzhu Yang & Jun Wang

  3. Key Laboratory of Biomedical Materials of Ministry of Education, South China University of Technology, Guangzhou, 510641, China

    Song Shen, Xianzhu Yang & Jun Wang

  4. National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou, 510006, China

    Song Shen, Xianzhu Yang & Jun Wang

  5. Hefei National Laboratory for Physical Science at Microscale, University of Science and Technology of China, Hefei, 230027, China

    Zhiting Cao & Jun Wang

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  1. Kaige Chen
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  2. Song Shen
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  3. Gui Zhao
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Correspondence to Xianzhu Yang or Jun Wang.

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Simultaneous elimination of cancer stem cells and bulk cancer cells by cationic-lipid-assisted nanoparticles for cancer therapy

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Chen, K., Shen, S., Zhao, G. et al. Simultaneous elimination of cancer stem cells and bulk cancer cells by cationic-lipid-assisted nanoparticles for cancer therapy. Nano Res. 11, 4183–4198 (2018). https://doi.org/10.1007/s12274-018-2007-y

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