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

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.