CuFe Layered Double Hydroxide as Self-Cascade Nanoreactor for Efficient Antibacterial Therapy

Nanozyme-induced reactive oxygen species (ROS)-dependent catalytic therapy has been developed into a powerful strategy against bacterial wound infections. However, the limited endogenous supply or instability of H₂O₂, the reliance on external stimuli for the generation of ROS, and the highly expressed glutathione (GSH) level make it a challenge to achieve high-performance therapeutic efficiency. In this work, a facile therapeutic strategy against bacterial infections with pristine CuFe layered double hydroxide (LDH) as the self-cascade nanoreactor is proposed without modification or additional energy input. CuFe LDH with an oxidase-like feature can catalyze the generation of multiple ROS, such as ¹O₂, ·O₂^-, and H₂O₂. And the self-generated H₂O₂ in the cascade nanoreactor could be further in situ transformed to ·OH owing to the peroxidase-like activity. As a result, the cell membrane of bacteria is destroyed, leading to death. Furthermore, its ultrahigh enzyme-like activity of CuFe LDH could effectively promote the breakdown of the biofilm structure. Additionally, the Cu²⁺-mediated GSH exhaustion of CuFe LDH further avoids the consumption of oxidized ROS and thereby significantly improves the sterilization effect. Finally, the as-prepared CuFe LDH with negligible side effects on normal tissues can be successfully used to eliminate the methicillin-resistant Staphylococcus aureus-infected wounds and accelerate their healing in the mouse model, which paves a new avenue as an antibacterial agent for clinical anti-infective treatment.