Nanozymes as Antibacterial Agents: New Concerns in Design and Enhancement Strategies.

Nanozymes exhibiting natural enzyme-mimicking catalytic activities as antibacterial agents present several advantages, including high stability, low cost, broad-spectrum antibacterial activity, ease of preparation and storage, and minimal bacterial resistance. Consequently, they have attracted significant attention in recent years. However, the rapid expansion of antimicrobial nanozyme research has resulted in pioneering reviews that do not comprehensively address emerging concerns and enhancement strategies within this field. This paper first summarizes the factors influencing the intrinsic activity of nanozymes; subsequently, we outline new research considerations for designing antibacterial nanozymes with enhanced functionality and biosafety features such as degradable, imageable, targeted, and bacterial-binding nanozymes as well as those capable of selectively targeting pathogenic bacteria while sparing normal cells and probiotics. Furthermore, we review novel enhancement strategies involving external physical stimuli (light or ultrasound), the introduction of extrinsic small molecules, and self-supplying H2O2 to enhance the activity of antibacterial nanozymes under physiological conditions characterized by low concentrations of H2O2 and O2. Additionally, we present non-redox nanozymes that operate independently of highly toxic reactive oxygen species (ROS) alongside those designed to combat less common pathogenic bacteria. Finally, we discuss current issues, challenges faced in the field, and future prospects for antibacterial nanozymes.