Nanohole-Array Induced Metallic Molybdenum Selenide Nanozyme for Photoenhanced Tumor-Specific Therapy

Deficient catalytic sensitivity to the tumor microenvironment is a major obstacle to nanozyme-mediated tumor therapy. Electron transfer is the intrinsic essence for a nanozyme-catalyzed redox reaction. Here, we developed a nanohole-array-induced metallic molybdenum selenide (n-MoSe2) that is enriched with Se vacancies and can serve as an electronic transfer station for cycling electrons between H2O2 decomposition and glutathione (GSH) depletion. In a MoSe2 nanohole array, the metallic phase reaches up to 84.5%, which has been experimentally and theoretically demonstrated to exhibit ultrasensitive H2O2 responses and enhanced peroxidase (POD)-like activities for H2O2 thermodynamic heterolysis. More intriguingly, plenty of delocalized electrons appear due to phase- and vacancy-facilitated band structure reconstruction. Combined with the limited characteristic sizes of nanoholes, the surface plasmon resonance effect can be excited, leading to the broad absorption spectrum spanning of n-MoSe2 from the visible to near-infrared region (NIR) for photothermal conversion. Under NIR laser irradiation, metallic MoSe2 is able to induce out-of-balance redox and metabolism homeostasis in the tumor region, thus significantly improving therapeutic effects. This study that takes advantage of phase and defect engineering offers inspiring insights into the development of high-efficiency photothermal nanozymes.