Ferroptosis mediated inhibition of breast cancer cells by β–elemene incorporated GSH/pH dual responsive nanomicelles

Ferroptosis represents a novel procedure of programmed cell death driven by iron-dependent lipid peroxidation, and may offer a promising strategy for cancer therapy. In this study, we developed poly (2-ethyl-2-oxazoline)-poly (lactic acid)-SS-poly (β-amino ester) (PEOz-PLA-SS-PBAE) loaded with β-elemene. The disulfide bond mediated depletion of glutathione (GSH) and inactivation of glutathione peroxidase 4 (GPX4) will lead to inactivation of the antioxidant system of the tumor cell, and β-elemene has the capacity to generate reactive oxygen species (ROS), and the above changes would induce a disruption of the redox balance within the tumor cell, resulting in ferroptosis of the tumor cell. In conclusion, in this study, water insoluble β-elemene was solubilized by the triblock copolymer to construct a pH/GSH dual-responsive nano-delivery system, and combined with iron death and chemotherapy to exert combinatory inhibition effect on breast cancer cells, which provides a new idea for the potential clinical application of β-elemene