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.

The intrinsic deficiencies of nanoparticle‐initiated catalysis for biomedical applications promote the fast development of alternative versatile theranostic modalities. The catalytic performance and selectivity are the critical issues that are challenging to be augmented and optimized in biological conditions. Single‐atom catalysts (SACs) featuring atomically dispersed single metal atoms have emerged as one of the most explored catalysts in biomedicine recently due to their preeminent catalytic activity and superior selectivity distinct from their nanosized counterparts. Herein, an overview of the pivotal significance of SACs and some underlying critical issues that need to be addressed is provided, with a specific focus on their versatile biomedical applications. Their fabrication strategies, surface engineering, and structural characterizations are discussed briefly. In particular, the catalytic performance of SACs in triggering some representative catalytic reactions for providing the fundamentals of biomedical use is discussed. A sequence of representative paradigms is summarized on the successful construction of SACs for varied biomedical applications (e.g., cancer treatment, wound disinfection, biosensing, and oxidative‐stress cytoprotection) with an emphasis on uncovering the intrinsic catalytic mechanisms and understanding the underlying structure–performance relationships. Finally, opportunities and challenges faced in the future development of SACs‐triggered catalysis for biomedical use are discussed and outlooked.

The hypoxic tumor microenvironment severely lowers the therapeutic efficacy of oxygen-dependent anticancer modalities because tumor hypoxia hinders the generation of toxic reactive oxygen species. Here we report a thermodynamic cancer-therapeutic modality that employs oxygen-irrelevant free radicals generated from thermo-labile initiators for inducing cancer cell death. A free radical nanogenerator was engineered via direct growth of mesoporous silica layer onto the surface of two-dimensional Nb 2 C MXene nanosheets toward multifunctionality, where the mesopore provided the reservoirs for initiators and the MXene core acted as the photonicthermal trigger at the near-infrared-II biowindow (NIR-II). Upon illumination by a 1064 nm NIR-II laser, the photothermal-conversion effect of Nb 2 C MXene induced the fast release and quick decomposition of the encapsulated initiators (AIPH) to produce free radicals, which promoted cancer cell apoptosis in both normoxic and hypoxic microenvironment. Systematic in vitro and in vivo evaluations have demonstrated the synergistic-therapeutic outcome of this intriguing photonic nanoplatform-enabled thermodynamic cancer therapy for completely eradicating the 4T1 tumors without recurrence by NIR-II laser irradiation. This work pioneers the thermodynamic therapy for oxygen-independent cancer treatment by photonic triggering at the NIR-II biowindow.