Engineering Dual Active Sites and Defect Structure in Nanozymes to Reprogram Jawbone Microenvironment for Osteoradionecrosis Therapy

Four to eight percent of patients with head and neck cancer will develop osteoradionecrosis of the jaw (ORNJ) after radiotherapy. Various radiation-induced tissue injuries are associated with reactive oxygen and nitrogen species (RONS) overproduction. Herein, Fe doping is used in VO_x (Fe-VO_x) nanozymes with multienzyme activities for ORNJ treatment via RONS scavenging. Fe doping can induce structure reconstruction of nanozymes with abundant defect production, including Fe substitution and oxygen vacancies (OVs), which markedly increased multiple enzyme-mimicking activity. Catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) enzyme-like performance of Fe-VO_x can effectively reprogram jawbone microenvironment to restore mitochondrial dysfunction and enhance mitophagy. Moreover, the surface plasmon resonance (SPR) effect of Fe-VO_x made it a good photothermal nanoagents for inhibiting jaw infection. Thus, this work demonstrated that Fe-VO_x nanozymes can efficiently scavenge RONS, activate mitophagy, and inhibit bacteria, which is potential for ORNJ treatment.