Enzyme-triggered on-demand release of a H2O2-self-supplying CuO2@Fe3O4 nanoagent for enhanced chemodyamic antimicrobial therapy and wound healing

Abstract

Nanoagents for chemodynamic therapy (CDT) hold a promising future in the field of antimicrobials, especially copper peroxide (CuO₂) (CP) nanomaterials which have garnered significant attention due to their ability to self-supply H₂O₂. Nevertheless, the poor stability of CuO₂ remains a critical challenge which restricts its practical application in the antibacterial field. In this study, an advanced nano-antimicrobial system HA-CP@Fe₃O₄ with enzyme-responsive properties is developed by coating hyaluronic acid (HA) on CuO₂-loaded iron tetraoxide nanoparticles. The coating of HA not only stabilizes the CuO₂ nanomaterials but also provides responsiveness towards the enzyme hyaluronidase, which is typically secreted by some bacteria. The outer layer of HA in HA-CP@Fe₃O₄ undergoes decomposition in the presence of hyaluronidase-secreting bacteria, resulting in the release of CuO₂@Fe₃O₄. The released CuO₂@Fe₃O₄ then self-supplies H₂O₂ 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 Fe₃O₄ allows the substance to be directed towards the infection site. Both in vitro and in vivo tests demonstrated that HA-CP@Fe₃O₄ 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.