Enzyme-triggered on-demand release of a H 2 O 2 -self-supplying CuO 2 @Fe 3 O 4 nanoagent for enhanced chemodyamic antimicrobial therapy and wound healing.

Nanoagents for chemodynamic therapy (CDT) hold a promising future in the field of antimicrobials, especially copper peroxide (CuO ₂ ) (CP) nanomaterials which have garnered significant attention due to their ability to self-supply H ₂ O ₂ . Nevertheless, the poor stability of CuO ₂ remains a critical challenge which restricts its practical application in the antibacterial field. In this study, an advanced nano-antimicrobial system HA-CP@Fe ₃ O ₄ with enzyme-responsive properties is developed by coating hyaluronic acid (HA) on CuO ₂ -loaded iron tetraoxide nanoparticles. The coating of HA not only stabilizes the CuO ₂ nanomaterials but also provides responsiveness towards the enzyme hyaluronidase, which is typically secreted by some bacteria. The outer layer of HA in HA-CP@Fe ₃ O ₄ undergoes decomposition in the presence of hyaluronidase-secreting bacteria, resulting in the release of CuO ₂ @Fe ₃ O ₄ . The released CuO ₂ @Fe ₃ O ₄ then self-supplies H ₂ O ₂ and generates reactive oxygen species (ROS) within the infected microenvironment through Fenton and Russell effects, to ultimately achieve effective and precise antimicrobial activity. Simultaneously, the magnetic property provided by Fe ₃ O ₄ allows the substance to be directed towards the infection site. Both in vitro and in vivo tests demonstrated that HA-CP@Fe ₃ O ₄ exhibited excellent antimicrobial capabilities at low concentration (30 μg mL ^-1 ), exceptional biocompatibility and the ability to accelerate wound healing. The findings of this work offer a new and promising approach for targeted and precise CDT.