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.