Reactive oxygen species (ROS) are generated and consumed in living organism for normal metabolism. Paradoxically, the overproduction and/or mismanagement of ROS have been involved in pathogenesis and progression of various human diseases. Here, we reported a two-dimensional (2D) vanadium carbide (V2C) MXene nanoenzyme (MXenzyme) that can mimic up to six naturally-occurring enzymes, including superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), glutathione peroxidase (GPx), thiol peroxidase (TPx) and haloperoxidase (HPO). Based on these enzyme-mimicking properties, the constructed 2D V2C MXenzyme not only possesses high biocompatibility but also exhibits robust in vitro cytoprotection against oxidative stress. Importantly, 2D V2C MXenzyme rebuilds the redox homeostasis without perturbing the endogenous antioxidant status and relieves ROS-induced damage with benign in vivo therapeutic effects, as demonstrated in both inflammation and neurodegeneration animal models. These findings open an avenue to enable the use of MXenzyme as a remedial nanoplatform to treat ROS-mediated inflammatory and neurodegenerative diseases.

Endogenic tumor chemodynamic therapy (CDT) is emerging as a tumor‐therapeutic strategy featuring in situ treatments with high efficiency and specificity based on the Fenton reaction principle. Considering the limitation of monotherapy and relatively insufficient intracellular level of endogenous hydrogen peroxide (H2O2) in tumor tissues, a mitochondria‐specific nanocatalyst composed of cisplatin prodrug and gallic acid‐ferrous (GA‐Fe(II)) nanocomposites is successfully fabricated to fulfill chemotherapy‐augmented sequential chemoreactive tumor therapy. The bioactive cisplatin elevates the level of endogenous H2O2 through the activation of nicotinamide adenine dinucleotide phosphate oxidase (NOX)‐related cascaded reactions, and the GA‐Fe(II) nanocomposites possessing sustainable Fenton catalytic activity subsequently catalyzes H2O2 into highly reactive and toxic hydroxyl radicals to substantially inhibit tumor progression. Especially, this mitochondria‐specific nanocatalyst amplifies oxidative stress, stimulates mitochondrial dysfunction, downregulates AKT/mTOR signaling and finally induces cell autophagic death. Both in vitro and in vivo measurements verify that the chemotherapy‐augmented sequential chemoreactive nanotherapy based on the mitochondria‐specific nanocatalyst implements excellent anticancer efficiency and avoids undesired side effects. This work reveals the enormous potential of chemotherapy‐augmented CDT for combating tumors.

Overcoming apoptosis resistance to achieve efficient breast cancer treatment remains a challenge. The precise induction of another form of programmed cell death, pyroptosis, is an excellent alternative for treating cancer. Ultrasound (US)‐enhanced enzyme dynamic (enzyodynamic) therapy is developed by employing LaFeO3 (LFO) perovskite nanocrystals as a substrate to increase the rate of deleterious reactive oxygen species (ROS) generation for intensive cell pyroptosis. LFO nanocrystals possess quadruple enzyme‐mimicking activities, including oxidase‐, peroxidase‐, glutathione peroxidase‐, and catalase‐mimicking activities, which undertake the dominant therapeutic task through cascade catalytic reactions, including the reversal of hypoxic microenvironment, depletion of endogenous glutathione, and continuous output of ROS. US exogenous stimulation increases the transition rate of the intermediate complex to Fe (II) and favors incremental ROS production, by which the ROS burst‐induced pyroptosis process is accomplished through the ROS‐TXNIP‐NLRP3‐GSDMD pathway. Both in vitro and in vivo antineoplastic outcomes affirm the ascendancy of LFO nanozyme‐induced pyroptosis. This work highlights the critical role of US coupled with nanocatalytic reactors in pyroptosis‐dominant breast cancer treatment with the apoptosis resistance circumvention feature.