Reactive oxygen species (ROS)-induced nanosystems represent one of the most essential, efficient, and encouraging nanobactericides for eliminating bacterial infection concerning the increasing resistance threats of existing antibiotics. Among them, Fenton-type metal peroxide nanoparticles are exciting nanomaterials with intriguing physiochemical properties, yet the study of this antimicrobial agent is still in its infancy. Herein, a robust pH-responsive Fenton nanosystem is constructed by the assembly of copper peroxide nanodots in pomegranate-like mesoporous silica nanoshells (CuO2@SiO2) that are capable of self-supplying H2O2 and sustainably generating O2. The enhanced antimicrobial performance is attributed to the pH responsiveness and excellent Fenton catalytic activity through either the Cu2+-catalyzed conversion of H2O2 to detrimental ROS under acid treatment or in situ O2 evolution in neutral media. Moreover, in vitro and in vivo investigations demonstrate that this nanocomposite can exhibit boosted antimicrobial capabilities and can significantly accelerate skin wound closure, while retaining outstanding cytocompatibility and hemocompatibility. Given its excellent physicochemical and antimicrobial properties, the broad application of this nanocomposite in bacteria-associated wound management is anticipated.

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