Biomimetic Nanoarchitectonics of Hollow Mesoporous Copper Oxide-Based Nanozymes with Cascade Catalytic Reaction for Near Infrared-II Reinforced Photothermal-Catalytic Therapy

Biomimetic nanozyme with natural enzyme-like activities has drawn extensive attention in cancer therapy, while its application was hindered by the limited catalytic efficacy in the complicated tumor microenvironment (TME). Herein, a hybrid biomimetic nanozyme combines polydopamine-decorated CuO with a natural enzyme of glucose oxidase (GOD), among which CuO is endowed with a high loading rate (47.1%) of GOD due to the elaborately designed hollow mesoporous structure that is constructed to maximize the cascade catalytic efficacy. In the TME, CuO could catalyze endogenous H₂O₂ into O₂ for relieving tumor hypoxia and improving the catalytic efficacy of GOD. Whereafter, the amplified glucose oxidation induces starvation therapy, and the generated H₂O₂ and H⁺ enhance the catalytic activity of CuO. Significantly, the tumor-specific chemodynamic therapy (CDT) could be realized when CuO degraded into Cu²⁺ in acidic and reductive TME. Furthermore, the photothermal therapy with high photothermal conversion efficiency (30.2%) is achieved under NIR-II laser (1064 nm) excitation, which could reinforce the generation of reactive oxygen species (•OH and •O₂^-). The TME initiates the biochemical reaction cycle of CuO, O₂, and GOD, which couples with an NIR-II-induced thermal effect to realize O₂-promoted starvation and photothermal-chemodynamic combined therapy. This hybrid biomimetic nanozyme enlightens the further development of nanozymes in multimodal cancer therapy.