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, s...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.展开更多
文摘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.
