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

作　　者：Kaige Chen Song Shen Gui Zhao Zhiting Cao Xianzhu Yang Jun Wang 

机构地区：[1]School of Life Sciences, University of Science and Technology of China, Hefei 230027, China [2]Institutes for Life Sciences, and School of Medicine, South China University of Technology, Guangzhou S 10006, China [3]Key Laboratory of Biomedical Materials of Ministry of Education, South China University of Technology, 6uangzhou S 1064 I, China [4]National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou 510006, China [5]Hefei National Laboratory for Physical Science at Microscale, University of Science and Technology of China, Hefei 230027, China [6]Kaige Chen and Song Shen contributed equally to this work.

出　　处：《Nano Research》2018年第8期4183-4198,共16页纳米研究（英文版）

摘　　要：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 elimin- ation of both CSCs and bulk cancer cells is necessary to improve therapeutic outcomes. Herein, we designed cationic-lipid-assisted nanopartides DTXLNPsRNA for simultaneous encapsulation of the conventional chemotherapeutic agent docetaxel （DTXL） and small interfering RNA （siRNA） targeting BMI-1 （siBMI-1）. We confirmed that nanopartides vrxLNPsiBMI-l effectively deliver both therapeutic agents into CSCs and bulk cancer cells. The bulk cancer cells were effectively killed by the DTXL encapsulated in DVXL NPsiBMI-1. In breast CSCs, BMI-1 expression was significantly downregulated by DVXLNpsiBMI-1; consequently, the sternness 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 kiUing of CSCs and bulk cancer cells in a murine model of an MDA-MB-231 orthotropic tumor.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 elimin- ation of both CSCs and bulk cancer cells is necessary to improve therapeutic outcomes. Herein, we designed cationic-lipid-assisted nanopartides DTXLNPsRNA for simultaneous encapsulation of the conventional chemotherapeutic agent docetaxel （DTXL） and small interfering RNA （siRNA） targeting BMI-1 （siBMI-1）. We confirmed that nanopartides vrxLNPsiBMI-l effectively deliver both therapeutic agents into CSCs and bulk cancer cells. The bulk cancer cells were effectively killed by the DTXL encapsulated in DVXL NPsiBMI-1. In breast CSCs, BMI-1 expression was significantly downregulated by DVXLNpsiBMI-1; consequently, the sternness 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 kiUing of CSCs and bulk cancer cells in a murine model of an MDA-MB-231 orthotropic tumor.

关 键 词：anti-cancer stem cells（CSCs） therap LBMI-1 combination therapy small interfering RNA（siRNA） therapy CO-DELIVERY 

分 类 号：Q813[生物学—生物工程] TQ174.759[化学工程—陶瓷工业]