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Nano Research

Article Title

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

Authors

Kaige Chen, School of Life Sciences, University of Science and Technology of China, Hefei 230027, China
Song Shen, Institutes for Life Sciences, and School of Medicine, South China University of Technology, Guangzhou 510006, China Key Laboratory of Biomedical Materials of Ministry of Education, South China University of Technology, Guangzhou 510641, China National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou 510006, China
Gui Zhao, School of Life Sciences, University of Science and Technology of China, Hefei 230027, China
Zhiting Cao, Hefei National Laboratory for Physical Science at Microscale, University of Science and Technology of China, Hefei 230027, China
Xianzhu Yang, Institutes for Life Sciences, and School of Medicine, South China University of Technology, Guangzhou 510006, China Key Laboratory of Biomedical Materials of Ministry of Education, South China University of Technology, Guangzhou 510641, China National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou 510006, China
Jun Wang, School of Life Sciences, University of Science and Technology of China, Hefei 230027, China Institutes for Life Sciences, and School of Medicine, South China University of Technology, Guangzhou 510006, China Key Laboratory of Biomedical Materials of Ministry of Education, South China University of Technology, Guangzhou 510641, China National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou 510006, China Hefei National Laboratory for Physical Science at Microscale, University of Science and Technology of China, Hefei 230027, China

Keywords

anti-CSCs therapy, BMI-1, combination therapy, siRNA therapy, co-delivery

Abstract

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 agent docetaxel (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.

Graphical Abstract

Publisher

Tsinghua University Press

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