Core@Shell MnO₂@MOF Nanozymes with Accelerated Oxygen Generation for Synergistic Chemodynamic and Starvation Therapy

High Resolution Image Download MS PowerPoint Slide One of the major factors that impedes the efficacy of glucose oxidase (GOx) during starvation therapy is the hypoxic-stricken environment in cancer cells. Herein, MnO 2 nanoparticles (NPs) are coated layer by layer with a ferric metal–organic framework (MOF) and loaded with a biocatalyst GOx to afford a core@shell nanozyme, MnO 2 @MOF@GOx, for synergistic reactions. In this platform, the shell material MOF not only acts as a nanocarrier for GOx loading but also can release iron ions for the Fenton reaction, leading to ferroptosis. Meanwhile, the GOx-catalyzed glucose oxidation consumes glucose for starvation therapy and promotes the intracellular acidity and H 2 O 2 supply, which are beneficial to the Fenton reaction. The H 2 O 2 produced during glucose depletion allows degradation of the MOF to facilitate the release of MnO 2, which then will timely react to H 2 O 2 and produce more oxygen to give more power to GOx for starvation therapy. MnO 2 @MOF@GOx can efficiently reduce the viability of 4T1 mammalian breast cancer, with an IC 50 of 4.3 μg/mL. Both in vitro and in vivo studies demonstrate that this nanozyme enables a remarkable anticancer therapeutic effect consisting of enhanced chemodynamic and starvation therapy due to the synergistic reactions.