Beyond antibiotics: engineered metal nanozymes for resistance-evading antibacterial therapy

Bacterial infections rank as the second leading cause of death globally, driven primarily by the alarming rise of multidrug-resistant (MDR) pathogens. These pathogens severely undermine the efficacy of conventional antibiotics and pose a grave threat to modern medical practice. To counter this urgent crisis, engineered metal nanozymes have emerged as a promising alternative therapeutic strategy. Leveraging their intrinsic enzyme-mimetic catalytic activity to generate bactericidal reactive oxygen species (ROS), metal nanozymes achieve potent broad-spectrum antibacterial action while minimizing the risk of resistance development. Beyond core ROS generation, these nanozymes employ sophisticated complementary mechanisms, including bioactive ion release and stimuli-responsive dual functionality. This multifaceted approach enables simultaneous pathogen eradication and protection of host tissue. Such unique therapeutic attributes, combined with high stability, persistent catalytic activity, favorable biocompatibility, precise tunability, and the potential for synergistic catalytic cascades, establish metal nanozymes as compelling candidates for next-generation antibacterial therapies. This review comprehensively summarizes the fundamental catalytic mechanisms underlying their antibacterial action and details advanced rational design strategies to optimize nanozyme performance. Furthermore, diverse metal-based nanozyme platforms for combating bacterial infections are classified and analyzed, highlighting recent advances in synergistic combination therapies that amplify therapeutic outcomes. Finally, we critically address persistent translational challenges and propose feasible strategies to advance these innovative platforms toward safe and effective clinical deployment against resistant infections.