γ‐Fe₂O₃ Loading Mitoxantrone and Glucose Oxidase for pH‐Responsive Chemo/Chemodynamic/Photothermal Synergistic Cancer Therapy

Abstract Traditional cancer therapy is limited by poor prognosis and risk of recurrence. Emerging therapies offer alternatives to these problems. In addition, synergistic therapy can combine the advantages of multiple therapies to eliminate cancer cells while attenuating damage to normal tissues. Herein, a theranostic nanoplatform based on the chemotherapeutic drug mitoxantrone (MTO) and glucose oxidase (GOx) co‐loaded γ‐Fe₂O₃ nanoparticles (MTO‐GOx@γ‐Fe₂O₃ NPs) is designed and prepared to realize photoacoustic imaging‐guided chemo/chemodynamic/photothermal (CT/CDT/PTT) synergistic cancer therapy. With a particle size of about 86.2 nm, the synthesized MTO‐GOx@γ‐Fe₂O₃ NPs can selectively accumulate at tumor sites by enhanced permeability and retention (EPR) effects. After entering cancer cells by endocytosis, MTO‐GOx@γ‐Fe₂O₃ NPs decompose into Fe³⁺ ions and release cargo because of their pH‐responsive characteristic. As a Food and Drug Administration (FDA)‐approved chemotherapy drug, MTO shows strong DNA disruption ability and satisfying photothermal conversion ability under laser irradiation for photothermal therapy. Simultaneously, GOx catalyzes the decomposition of glucose and generates hydrogen peroxide (H₂O₂) to enhance the chemodynamic therapy efficiency. In vitro and in vivo experiments reveal that MTO‐GOx@γ‐Fe₂O₃ NPs possess a significant synergistic therapeutic effect in cancer treatment.