A Multifunctional Fe‐Based Metal–Organic Framework With Ferroptosis for Synergistic Therapy

ABSTRACT Generally, single cancer treatment is insufficient to achieve ideal therapeutic effect. Multimodal therapy has the potential to overcome efficacy challenges and reveals great promise in enhancing therapeutic effect. Herein, a combination treatment system (DOX@Fe‐PBC) based on chemotherapy, chemodynamic therapy (CDT), and ferroptosis was constructed by loading anticancer drug doxorubicin hydrochloride (DOX) into Fe‐based metal–organic framework (Fe‐PBC). In simulated tumor microenvironment, the system released anticancer drug DOX to be a DNA intercalator and topoisomerase II inhibitor to realize chemotherapy (CT) and iron ions were delivered to induce Fenton reaction, which boost the generation of •OH, resulting in the enhancement of the effect of chemodynamic therapy (CDT). Meantime, the system could consume glutathione (GSH) to reduce the expression of glutathione peroxidase 4 (GPX4); then, lipid peroxides (LPO) were accumulated to realize ferroptosis. DOX@Fe‐PBC provided an effective strategy of chemotherapy, CDT, and ferroptosis to realize ideal cancer treatment.