Cobalt Single‐Atom Intercalation in Molybdenum Disulfide Enhances Piezocatalytic and Enzyodynamic Activities for Advanced Cancer Therapeutics

Abstract Piezoelectric semiconductor nanomaterials have attracted considerable interest in piezocatalytic tumor treatment. However, piezocatalytic therapy encounters obstacles such as suboptimal piezoelectric responses, rapid electron‐hole recombination, inefficient energy harvesting, and the complexities of the tumor microenvironment. In this study, sulfur vacancy‐engineered cobalt (Co) single‐atom doped molybdenum disulfide (SA‐Co@MoS 2 ) nanoflowers are strategically designed, which exhibit enhanced piezoelectric effects. Specifically, the introduction of Co single atom not only induces lattice distortion and out‐of‐plane polarization but also leads to the formation of numerous sulfur vacancies. These changes collectively narrow the intrinsic bandgap of the material, facilitating effective separation and migration of charge carriers, and enabling efficient production of reactive oxygen species under ultrasound stimulation. Additionally, the SA‐Co@MoS 2 nanoflowers demonstrate improved enzymatic activity and exhibit glutathione depletion capabilities attributed to the mixed valence states of Co, intensifying oxidative stress in tumor cells, and leading to cell cycle arrest and apoptosis, while the inactivation of glutathione peroxidase 4 induces ferroptosis. Both in vitro and in vivo results indicate that SA‐Co@MoS 2 nanoflowers can significantly eliminate tumor cells. This study offers valuable insights into the exploration of single‐atom doping‐enhanced piezoelectric sonosensitizers for cancer treatment, potentially paving the way for advancements in the field of piezocatalytic synergistic enzyodynamic therapy.