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

Abstract

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.

Nanotechnological strategies to increase the oxygen content of the tumor

“…With the action of oxygen and GOx, glucose can be converted into gluconic acid and H 2 O 2 , thereby cutting off the nutrition source of tumor cells and inhibiting cancer cell proliferation ( Huo et al, 2017 ; Xu et al, 2022c ; Wang et al, 2022f ). Considering that the catalytic activity of a single enzyme is insufficient to achieve satisfactory therapeutic effects, the development of nanozymes with multiple enzyme-mimetic functions is necessary.…”

Turning Silica into Enzymes by Hydrogenation: Simultaneously Achieving Oxygen Vacancy Engineering and Tumor Adaptive Accumulation for NIR‐II‐Potentiated Therapy

“…To further imitate temperature variations caused by the photothermal effect of HMMSNs nanozymes, the reaction solutions were kept at 37 °C (control) and 51 °C (photothermal group). [ 42 ] As revealed by the UV–vis absorption curves in Figure 4b, a notable drop in MB absorbance at 51 °C confirmed that the NIR‐II‐induced hyperthermia will enhance POD‐like effect of HMMSNs. Meanwhile, the degradation of MB was also promoted as the GSH and H 2 O 2 levels increased from 0 to 10 mM under weakly acidic condition (Figure S17a,b, Supporting Information).…”

Nanomedicine Strategies in Conquering and Utilizing the Cancer Hypoxia Environment

“…Wang et al designed and synthesized a hollow mesoporous copper oxide (HMC), loaded substantial GOD, and modified with polydopamine for the enhancement of hydrophilicity and biocompatibility (HMCGP). 224 At the hypoxic tumor site, the HMCGP could produce O 2 by decomposition of H 2 O 2 to alleviate the tumor hypoxia and enhance the catalytic activity of GOD. Meanwhile, the oxidation of glucose-induced decline of pH and increase of H 2 O 2 can induce a cascade enzyme reaction to maximize the catalytic efficiency of HMCGP.…”

“…Metal oxide nanoenzymes, such as CuO, MnO 2 , and CeO 2 , are promising in catalyzing the O 2 production reaction of endogenous H 2 O 2 to relieve tumor hypoxia. Wang et al designed and synthesized a hollow mesoporous copper oxide (HMC), loaded substantial GOD, and modified with polydopamine for the enhancement of hydrophilicity and biocompatibility (HMCGP) . At the hypoxic tumor site, the HMCGP could produce O 2 by decomposition of H 2 O 2 to alleviate the tumor hypoxia and enhance the catalytic activity of GOD.…”