Sequential Catalytic, Magnetic Targeting Nanoplatform for Synergistic Photothermal and NIR-Enhanced Chemodynamic Therapy

Tailored to the peculiar tumor microenvironment, Fenton reaction-based chemodynamic therapy (CDT) has attracted considerable attention for tumor treatment. However, the efficacy of CDT is highly limited by both H 2 O 2 overproduction and the low activity of catalysts at the tumor site. Herein, a novel magnetic targeting nanoplatform (γ-Fe 2 O 3 -GOx-DMSN) has been designed by simply depositing ultrasmall γ-Fe 2 O 3 nanoparticles and natural glucose oxidase (GOx) into the large mesopores (∼13 nm) of dendritic mesoporous silica (DMSN) spheres for near-infrared (NIR) light-enhanced CDT efficacy. In this structure, GOx can effectively consume glucose in the tumor cells to induce a decrease in the pH value and generate a considerable amount of H 2 O 2, both of which promote subsequent Fenton reaction. These ultrasmall γ-Fe 2 O 3 nanoparticles not only serve as an efficacious Fenton catalyst for degradation of the increased H 2 O 2 within the tumor to produce highly toxic hydroxyl radicals ( • OH) but also exhibit high photothermal therapy (PTT) efficiency upon irradiation with 808 nm light. Importantly, the generated hypothermia can significantly accelerate the Fenton process, thereby enabling a synergetic PTT/hypothermia-enhanced CDT effect. Our work manifests a proof of concept of H 2 O 2 -evolving and NIR-enhanced CDT, providing a new perspective for cancer therapy.