Rational Engineering of Antibiofilm Nanozymes: From Catalytic Mechanisms to Multimodal Therapeutic Strategies

Bacterial biofilms, characterized by their complex three-dimensional architectures and drug resistance, represent a critical bottleneck leading to the failure of conventional antibacterial therapies. Recently, nanozymes have emerged as a promising solution. By generating reactive species in situ or specifically cleaving chemical bonds, nanozymes overcome the limitations of single-target strategies through multi-mechanistic synergy and tunable catalytic performances. This enables multidimensional interventions for biofilm disruption and bacterial inactivation. This review systematically outlines the evolutionary trajectory of antibiofilm nanozymes, with a particular emphasis on elucidating their core catalytic mechanisms and structure– activity relationships. Specifically, oxidoreductase-like nanozymes modulate reactive oxygen species bursts to trigger bacterial membrane disruption, genetic material damage, and metabolic collapse. Regarding hydrolytic mechanisms, a multi-target synergistic hydrolysis strategy is emphatically detailed, involving the construction of four distinct functional classes of nanozymes: nuclease-, protease-, glycosidase-, and esterase-mimicking systems. Utilizing surface-exposed Lewis acid sites, these nanozymes precisely target and degrade key components of the extracellular polymeric substance and quorum sensing molecules, dismantling the physical barriers of biofilms. Furthermore, external-field-responsive interventions, including optical, acoustic, electrical, and magnetic stimuli, can remodel the mass transport microenvironment and achieve spatiotemporal augmentation of catalytic performances. Finally, evolutionary trajectories are proposed for constructing next-generation intelligent nanotherapeutic platforms via multienzyme cascades. The prevailing challenges are summarized in standardized activity evaluation and clinical translation, and envision the frontier trends of integrating artificial intelligence with theoretical calculations to drive the paradigm shift from empirical “trial-and-error” approaches to mechanism-driven rational design, potentially providing a robust theoretical foundation for developing advanced antiinfective materials.