Multienzyme-Activity Sulfur Quantum Dot Nanozyme-Mediated Cascade Reactions in Whole-Stage Symptomatic Therapy of Infected Bone Defects

Integrating the therapeutic efficacy of early bacterial clearance, midstage inflammatory remission, and late-stage effective tissue healing is considered a pivotal challenge in symptomatic treatment of infected bone defects (IBDs). Herein, a microenvironment-adaptive nanoplatform based on a sulfur quantum dot (SQD) nanozyme was proposed for whole-stage symptomatic therapy of IBDs by mediating the sequence of enzyme cascade reactions. The SQD nanozyme prepared by a size-engineering modification strategy exhibits enhanced multienzyme activity compared to conventional micrometer- and nanometer-sized sulfur particles. In the early stages of bacterial infection, the SQD nanozyme self-activates superoxide dismutase-peroxidase activity, resulting in the production of reactive oxygen species (ROS) that effectively eliminate bacteria. After disinfection, the SQD nanozyme self-switched to superoxide dismutase-catalase mimetic behavior and eliminated excess ROS, efficiently promoting macrophage polarization to an anti-inflammatory phenotype in the midinflammatory microenvironment. Importantly, SQD nanozyme-mediated M2 macrophage polarization significantly improved the damaged bone immune microenvironment, accelerating bone repair at late-stage tissue healing. Therefore, this strategy offers a promising and viable approach for the treatment of infectious tissue healing by developing multienzyme-activity nanozymes that respond intelligently to the microenvironment at different stages, effectively fighting bacteria, reducing inflammation, and promoting tissue regeneration for whole-stage symptomatic therapy.