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

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Abstract
Cancer Stem Cells (CSCs) are a subpopulation of tumor cells which exhibits self-renewal, differentiation and tumorigenicity. CSCs are highly resistant to 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 and evidenced by in vitro and in vivo tumor models. Here, salinomycin was conjugated with biocompatible gold nanoparticles (AuNPs) coated with poly(ethylene glycol) (PEG) to improve its specificity in targeting breast cancer stem cells (BCSC). BCSC derived from CD24low/CD44high subpopulation showed high sensitivity to Sal-AuNPs treatment. 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-AuNPs is an efficient therapeutic avenue in eliminating cancer stem cells.
Funding Information
  • National Health and Medical Research Council (1112258)

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