Sequential catalytic nanomedicine augments synergistic chemodrug and chemodynamic cancer therapy

The tumor microenvironment (TME) provides intriguing features/indications for rational design of diverse therapeutic protocols with high tumor specificity and therapeutic efficacy. In this work, we report the introduction of the sequential catalytic concept into theranostic nanomedicine for cancer-specific therapy, which has been achieved by the construction of glucose oxidase (GOD) and Mitomycin C (MMC) co-loaded superparamagnetic iron oxide nanoparticles (designated as SMG nanocatalysts). Based on the large amounts of glucose in tumors, the GOD component in SMG catalyzes glucose to convert into hydrogen peroxide (H2O2) and gluconic acid with the simultaneous consumption of oxygen. The post-produced H2O2 is further catalyzed by iron oxide in SMG to produce large amounts of highly toxic hydroxyl radicals for cancer therapy, and the generated gluconic acid enhances such a Fenton-based catalytic reaction. On the other hand, the loaded MMC drug is activated because of the consumption of oxygen and enhanced hypoxia in tumors, causing high chemotherapeutic efficacy. Based on the high synergistic chemodrug and chemodynamic therapeutic efficacy in combating cancer, cancer cells are efficiently killed and tumor growth is thus significantly suppressed. This work paves a new way for cancer therapy by taking into account the full features and advantages of the TME and the physiochemical properties of the chosen nanocatalysts, which also links nanocatalytic science and nanomedicine for proposing new efficient tumor-therapeutic modalities.