Reactive oxygen species (ROS) plays important roles in living organisms. While ROS is a double-edged sword, which can eliminate drug-resistant bacteria, but excessive levels can cause oxidative damage to cells. A core–shell nanozyme, CeO₂@ZIF-8/Au, has been crafted, spontaneously activating both ROS generating and scavenging functions, achieving the multi-faceted functions of eliminating bacteria, reducing inflammation, and promoting wound healing. The Au Nanoparticles (NPs) on the shell exhibit high-efficiency peroxidase-like activity, producing ROS to kill bacteria. Meanwhile, the encapsulation of CeO₂ core within ZIF-8 provides a seal for temporarily limiting the superoxide dismutase and catalase-like activities of CeO₂ nanoparticles. Subsequently, as the ZIF-8 structure decomposes in the acidic microenvironment, the CeO₂ core is gradually released, exerting its ROS scavenging activity to eliminate excess ROS produced by the Au NPs. These two functions automatically and continuously regulate the balance of ROS levels, ultimately achieving the function of killing bacteria, reducing inflammation, and promoting wound healing. Such innovative ROS spontaneous regulators hold immense potential for revolutionizing the field of antibacterial agents and therapies.

The abuse of antibiotics makes bacterial infection an increasingly serious global health threat. Reactive oxygen species (ROS) are the ideal alternative antibacterial approach for quick and effective sterilization. Although various antibacterial strategies based on ROS have been developed, many of them are still limited by insufficient antibacterial efficiency. Here, we have developed an acid-enhanced dual-modal antibacterial strategy based on zeolitic imidazolate frameworks-8 (ZIF8) -derived nanozyme. ZIF8, which can release Zn²⁺, is chosen as the carrier to integrate glucose oxidase (GOx) and gold nanoparticles (Au NPs) which can produce ROS via a cascade catalytic reaction. Thus, the bactericidal capability of ROS and Zn²⁺ have been integrated. More importantly, gluconic acid, a “by-product” of the catalytic reaction, can generate an acidic environment to promote both the ROS-producing and Zn²⁺-releasing, enhancing the overall antibacterial performance further. This triple-synergistic strategy exhibits extraordinary bactericidal ability at a low dosage of 4 μg/mL (for S. aureus) and 8 μg/mL (for E. coli), which shows a great potential of MOF-derived nanozyme for efficient bacterial eradication and diverse biomedical applications.