Self-Adaptive Antibiofilm Effect and Immune Regulation by Hollow Cu₂MoS₄ Nanospheres for Treatment of Implant Infections

Implant infections are difficult to cure by traditional antibiotic therapy due to bacterial biofilm-induced antibiotic tolerance and impaired immune responses. To efficiently treat implant infections, therapeutic agents need to kill bacteria and regulate the inflammatory response of immune cells during the biofilm elimination process. Herein, multifunctional smart hollow Cu 2 MoS 4 nanospheres (H-CMS NSs) with pH-responsive enzyme-like activities were prepared for self-adaptively eliminating biofilms and regulating the inflammation of macrophages in implant infections. During biofilm infection, the tissue microenvironment around implants is acidic. H-CMS NSs with oxidase (OXD)/peroxidase (POD)-like activities can catalyze reactive oxidative species (ROS) generation for directly killing bacteria and polarizing macrophages to a proinflammatory phenotype. Moreover, the POD-like activity and antibacterial property of H-CMS NSs can be further enhanced under ultrasound (US) irradiation. After the elimination of biofilms, the tissue microenvironment around implants shifts from acidic to neutral. H-CMS NSs show catalase (CAT)-like activity and eliminate excessive ROS, which polarizes macrophages to anti-inflammatory phenotype and promotes healing of infected tissue. This work provides a smart nanozyme with self-adaptive regulation of the antibiofilm activity and immune response by regulating ROS generation/elimination according to the different pathological microenvironments in implant infections during the different therapeutic stages.