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.
Keywords: NIR-II laser; cascade enzyme reaction; nanozyme; photothermal−chemodynamic therapy; starvation therapy.