Mitophagy activation for jawbone radiation injury therapy via angiogenesis/osteogenesis-active nanozymes.

Radiotherapy-induced osteoradionecrosis of the jaw (ORNJ) affects quality of life by causing severe pain, persistent infections, and stomatognathic dysfunction. Current ORNJ treatments are limited by several factors, including surgical trauma and notable individual differences. Oxidative stress, which is a critical driver of radiation-induced injury, promotes inflammation and disrupts the balance between bone formation and resorption. Here, we developed ceria-doped silicate nanozymes (CeSNs) to eliminate reactive oxygen species (ROS) by inducing a superoxide dismutase-like (SOD-like) and catalase-like (CAT-like) cascade. ROS-eliminating mitophagy contributed to the restoration of jawbone radiation injury. Dl-3-n-butylphthalide (NBP) encapsulated in CeSNs (NBP@CeSNs) demonstrated improved pH-responsive release for enhanced angiogenesis, while the silicon ions of silicate enhanced jawbone osteogenesis, thus providing the nanozymes with angiogenesis and osteogenesis capabilities. Our NBP@CeSNs nanozymes provided a promising pathway for ORNJ treatment.