Rod-shape inorganic biomimetic mutual-reinforcing MnO₂-Au nanozymes for catalysis-enhanced hypoxic tumor therapy

Biomimetic nanozymes possessing natural enzyme-mimetic activities have been extensively applied in nanocatalytic tumor therapy. However, engineering hybrid biomimetic nanozymes to achieve superior nanozyme activity remained to be an intractable challenge in hypoxic tumors. Herein, a rod-like biomimetic hybrid inorganic MnO₂-Au nanozymes are developed, where MnO₂ and ultrasmall Au nanoparticles (NPs) are successively deposited on the mesoporous silica nanorod to cooperatively improve the O₂ content and thermal sensitivity of hypoxic solid tumors guided by multi-modal imaging. Under the catalyzing of MnO₂, the intratumoral H₂O₂ is decomposed to greatly accelerate O₂ generation, which could boost the curative effect of radiation therapy (RT) and further enhance the Au-catalyzed glucose oxidation. Mutually, the Au NPs can steadily and efficiently catalyze the oxidation of glucose in harsh tumor microenvironment, thus sensitizing tumor cells to thermal ablation for mild photothermal therapy and further promoting the catalytic efficiency of MnO₂ with the self-supplied H₂O₂/H⁺. As a result, this mutual-reinforcing cycle can endow the nanoplatform with accelerated O₂ generation, thus alleviating hypoxic environment and further boosting RT effect. Furthermore, acute glucose consuming can induce downregulation expression of heat shock protein (HSP), achieving starvation-promoted mild photothermal therapy. This synthesized hybrid nanozymes proves to be a versatile theranostic agent for nanocatalytic cancer therapy.