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 H2O2 overproduction and the low activity of catalysts at the tumor site. Herein, a novel magnetic targeting nanoplatform (gamma-Fe2O3-GOx-DMSN) has been designed by simply depositing ultrasmall gamma-Fe2O3 nanoparticles and natural glucose oxidase (GOx) into the large mesopores (similar to 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 H2O2, both of which promote subsequent Fenton reaction. These ultrasmall gamma-Fe2O3 nanoparticles not only serve as an efficacious Fenton catalyst for degradation of the increased H2O2 within the tumor to produce highly toxic hydroxyl radicals ((OH)-O-center dot) 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 H2O2-evolving and NIR-enhanced CDT, providing a new perspective for cancer therapy.