Electric Field-Empowered Nanozymes: From Passive Adaptation to Active Precision Therapy

The clinical translation of nanozymes is hindered by the passive and uncontrollable catalytic properties, necessitating active and precise spatiotemporal regulation. Inspired by the electrostatic preorganization theory of efficient natural enzymes, this review provides a systematic analysis of electric field-regulated nanozymes. Compared to conventional physical stimuli, this approach offers a tunable and complementary framework for active precise therapy. Diverse electrical input modes provide adaptable driving forces for precisely regulating nanozyme catalysis across various biomedical scenarios. Furthermore, at the atomic scale, the underlying mechanisms are elucidated, demonstrating how the electric field inputs optimize the d-band center, surface charges, band structure, and active sites to promote substrate adsorption and lower reaction energy barriers, thereby enhancing the catalytic effect. To maximize electric field-nanozyme coupling, design principles for a complete charge pathway are distilled: optimizing intrinsic field response, directional charge rectification, and achieving low-loss transport. Subsequently, the applications of electric field-regulated nanozymes in precision therapy are summarized, including on-demand spatiotemporal activation, quantitative dosage regulation, and active microenvironment remodeling. Finally, this review highlights the immense potential of interdisciplinary integration in overcoming the biosafety and mechanism bottlenecks of this regulation strategy. These insights provide a new perspective for advancing electric field-regulated nanozymes toward precision therapy.