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

Synergistictherapeutic nanomedicine with great biosafety was regardedas a promising strategy for cancer therapy in clinic. Due to the drugresistance and insufficient performance of chemotherapy, the responserate in non-small cell lung cancer is limited. As another effectivestrategy against tumor, ferroptosis may enhance the sensitivity ofchemotherapy. Herein, we reported a biomimetic iron metal-organicframework (Fe-MOF) nanomedicine responding to the intracellular environmentof non-small cell lung cancer therapy to accelerate tumor cell deathby inducing the ferroptosis and apoptosis of tumor cells. We demonstratedthat the doxorubicin (DOX)-loaded biomimetic Fe-MOF (mFe-MOFDOX) could dramatically promote degradation for Fe2+ generationand release of DOX in the intracellular acidic microenvironment. ThemFe-MOFDOX nanoparticles enhanced the generation of reactiveoxygen species (ROS) to induce comparable glutathione peroxidase 4(GPX4)-mediated ferroptosis and assisted DOX-mediated apoptosis. Eventually,the combination of biomimetic nanoparticle-induced ferroptosis andchemotherapy-induced apoptosis inhibited tumor growth and lung metastasis,suggesting the promising potential of ferroptosis induction for promotingnon-small cell lung cancer chemotherapy.