Space-Selective Chemodynamic Therapy of CuFeO Nanocubes for Implant-Related Infections.

Implant-related infections (IRIs) are a serious complication after orthopedic surgery, especially when a biofilm develops and establishes physical and chemical barriers protecting bacteria from antibiotics and the hosts local immune system. Effectively eliminating biofilms is essential but difficult, as it requires not only breaking the physical barrier but also changing the chemical barrier that induces an immunosuppressive microenvironment. Herein, tailored to a biofilm microenvironment (BME), we proposed a space-selective chemodynamic therapy (CDT) strategy to combat IRIs using metastable CuFeO nanocubes (NCs) as smart Fenton-like reaction catalysts whose activity can be regulated by pH and HO concentration. In the biofilm, extracellular DNA (eDNA) was cleaved by high levels of hydroxyl radicals (•OH) catalyzed by CuFeO NCs, thereby disrupting the rigid biofilm. Outside the biofilm with relatively higher pH and lower HO concentration, lower levels of generated •OH effectively reversed the immunosuppressive microenvironment by inducing pro-inflammatory macrophage polarization. Biofilm fragments and exposed bacteria were then persistently eliminated through the collaboration of pro-inflammatory immunity and •OH. The spatially selective activation of CDT and synergistic immunomodulation exerted excellent effects on the treatment of IRIs and The anti-infection strategy is expected to provide a method to conquer IRIs.