Salinomycin-Loaded Gold Nanoparticles for Treating Cancer Stem Cells by Ferroptosis-Induced Cell Death

Cancer stem cells (CSCs) are a subpopulation of tumor cells that exhibit self-renewal, differentiation, and tumorigenicity. CSCs are highly resistant to the conventional cancer treatment and have been associated with metastasis. Several studies have been shown that salinomycin (Sal) has the potential to target cancer stem cells evidenced by in vitro and in vivo tumor models. Here, salinomycin was conjugated with biocompatible gold nanoparticles (AuNPs) coated with poly(ethylene glycol) to improve its specificity in targeting breast cancer stem cells (BCSCs). BCSCs derived from CD24low/CD44high subpopulation showed high sensitivity to Sal–AuNP treatment. An in-depth analysis on the mechanism of action of Sal–AuNPs indicated ferroptosis, an iron-dependent cell death, was achieved as a result of iron accumulation and inhibition of antioxidant properties. This also led to the induction of oxidative stress, mitochondrial dysfunction, and lipid oxidation. Our findings suggest Sal–AuNP treatment is an efficient therapeutic avenue in eliminating cancer stem cells.