Self-evolved hydrogen peroxide boosts photothermal-promoted tumor-specific nanocatalytic therapy

The emerging nanocatalytic tumor therapy such as chemodynamic therapy (CDT) converts less harmful hydrogen peroxide (H₂O₂) into highly toxic hydroxyl radicals (˙OH) via metal ion-mediated catalytic Fenton chemistry, which has motivated extensive research interest due to the high specificity of the nanocatalytic reactions to the tumor microenvironment (TME) and minimized side effects. However, traditional CDT substantially suffers from the insufficiency of intratumoral H₂O₂ for inducing a satisfactory therapeutic efficacy. In this work, we report on a photothermally-promoted Fenton reaction triggered by self-supplied H₂O₂, based on the constructed two-dimensional (2D) multifunctional therapeutic Nb₂C–IO–CaO₂ nanoreactors with enhanced therapeutic efficacy and therapeutic biosafety. These Nb₂C–IO–CaO₂ nanoreactors employ calcium peroxide (CaO₂) as a potent H₂O₂ supplier to sustain the iron oxide (IO) nanoparticle-mediated catalytic Fenton reaction, and to liberate highly toxic ˙OH for inducing tumor-cell apoptosis. Meanwhile, the intratumoral ˙OH production was further promoted by the photothermal effect of the Nb₂C–IO–CaO₂ nanoreactors under near infrared irradiation at the second biowindow. Extensive in vitro and in vivo evaluations have demonstrated significantly enhanced reactive oxygen species (ROS) production and an outstanding photothermal effect based on these Nb₂C–IO–CaO₂ nanoreactors, which synergistically lead to elevated therapeutic efficacy. Therefore, this work not only exhibits a promising prospect for reforming the TME to achieve enhanced Fenton reactivity for CDT by elaborately designed nanomaterials with multifunctionality, but also provides novel efficient cancer-therapeutic modalities with simultaneous high therapeutic efficacy and low side effects.