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.