Reactive Oxygen Species- and Cell-Free DNA-Scavenging Mn₃O₄ Nanozymes for Acute Kidney Injury Therapy

Abstract

Reactive oxygen species (ROS) scavenging therapy toward acute kidney injury (AKI) is promising, but no effective ROS scavenging drug has been developed yet. Moreover, cell-free DNA (cfDNA) is also involved in AKI, but the corresponding therapies have not been well developed. To tackle these challenges, Mn₃O₄ nanoflowers (Nfs) possessing both ROS and cfDNA scavenging activities were developed for better AKI protection as follows. First, Mn₃O₄ Nfs could protect HK2 cells through cascade ROS scavenging (dismutating ^·O₂^- into H₂O₂ by superoxide dismutase-like activity and then decomposing H₂O₂ by catalase-like activity). Second, Mn₃O₄ Nfs could efficiently adsorb cfDNA and then decrease the inflammation caused by cfDNA. Combined, remarkable therapeutic efficacy was achieved in both cisplatin-induced and ischemia-reperfusion AKI murine models. Furthermore, Mn₃O₄ Nfs could be used for the <i>T</i>₁-MRI real-time imaging of AKI. This study not only offered a promising treatment for AKI but also showed the translational potential of nanozymes.