Enzyme-triggered on-demand release of a HO-self-supplying CuO@FeO 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) (CP) nanomaterials which have garnered significant attention due to their ability to self-supply HO. Nevertheless, the poor stability of CuO remains a critical challenge which restricts its practical application in the antibacterial field. In this study, an advanced nano-antimicrobial system HA-CP@FeO with enzyme-responsive properties is developed by coating hyaluronic acid (HA) on CuO-loaded iron tetraoxide nanoparticles. The coating of HA not only stabilizes the CuO nanomaterials but also provides responsiveness towards the enzyme hyaluronidase, which is typically secreted by some bacteria. The outer layer of HA in HA-CP@FeO undergoes decomposition in the presence of hyaluronidase-secreting bacteria, resulting in the release of CuO@FeO. The released CuO@FeO then self-supplies HO 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 FeO allows the substance to be directed towards the infection site. Both and tests demonstrated that HA-CP@FeO exhibited excellent antimicrobial capabilities at low concentration (30 μg mL), 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.