Fe-Based Metal–Organic Frameworks with Ferroptosis Generation Ability for Remodeling Chemotherapy of Non-small Cell Lung Cancer

Synergistic therapeutic nanomedicine with great biosafety was regarded as a promising strategy for cancer therapy in clinic. Due to the drug resistance and insufficient performance of chemotherapy, the response rate in non-small cell lung cancer is limited. As another effective strategy against tumor, ferroptosis may enhance the sensitivity of chemotherapy. Herein, we reported a biomimetic iron metal–organic framework (Fe-MOF) nanomedicine responding to the intracellular environment of non-small cell lung cancer therapy to accelerate tumor cell death by inducing the ferroptosis and apoptosis of tumor cells. We demonstrated that the doxorubicin (DOX)-loaded biomimetic Fe-MOF (mFe-MOFDOX) could dramatically promote degradation for Fe2+ generation and release of DOX in the intracellular acidic microenvironment. The mFe-MOFDOX nanoparticles enhanced the generation of reactive oxygen species (ROS) to induce comparable glutathione peroxidase 4 (GPX4)-mediated ferroptosis and assisted DOX-mediated apoptosis. Eventually, the combination of biomimetic nanoparticle-induced ferroptosis and chemotherapy-induced apoptosis inhibited tumor growth and lung metastasis, suggesting the promising potential of ferroptosis induction for promoting non-small cell lung cancer chemotherapy.