The Sustainability of Energy Conversion Inhibition for Tumor Ferroptosis Therapy and Chemotherapy

Abstract The hyperactive energy metabolism mostly contributes the tumor cells growth and proliferation. Herein, the intelligent nanoparticles (P‐B‐D NPs) obtained by loading BAY‐876 and doxorubicin (Dox)‐Duplex into nanoparticles composed of disulfide bond (SS) containing polymer are reported, which provide an efficient resistance of tumor cells energy metabolism and tumor growth to conquer malignant tumor. In response to the reducing microenvironment of tumor tissue, the SS bond can be disintegrated by intracellular glutathione to block the synthesis of lipid repair enzyme‐glutathione peroxidase 4 for ferroptosis therapy. More importantly, the released BAY‐876 can inhibit the functionality of glucose transporter 1, restricting the glucose uptake of tumor cells to a low energy metabolism status. Meanwhile, Dox‐Duplex can interact with ATP to reduce intracellular ATP content and release Dox to kill tumor cells. Collectively, this work offers a new idea for restricting tumor cells energy metabolism to inhibit their proliferation.