Metal-free multifunctional nanozymes mimicking endogenous antioxidant system for acute kidney injury alleviation

Cellular redox homeostasis is highly dependent on endogenous antioxidant systems, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). The nanozymes mimicking the catalytic activities of natural antioxidant systems serve as potential candidates for the therapy of reactive oxygen species (ROS)-related diseases. However, previously reported metal-containing nanozymes possessed unsatisfactory catalytic activity and inevitable peroxidase activity, limiting their translational applications. Therefore, inspired by the superior ROS scavenging activities of natural polyphenols and metal-free carbon dots (CDs) with ultra-small size, phenol-functionalized CDs that mimic endogenous antioxidant system have been fabricated. The SOD activity was determined at an extremely high level (18187 U/mg), which was substantially comparable to natural SOD. Notably, this study reveals for the first time that CDs, as selenium-free nanomaterials, show robust GPx activity in vitro. The theory calculation suggests that the bond dissociation of phenols on CDs is considerably lower than selenocysteine of natural GPx, which facilitates the formation of peroxide intermediate to initiate GPx-like reactions. Furthermore, the kidney-targeting and intracellular antioxidant mimicking properties contribute to the effective alleviating cisplatin-induced acute kidney injury via suppressing oxidative stress-mediated ferroptosis in vivo. These results provide an effective polyphenol-functionalized strategy for synthesizing metal-free multifunctional antioxidant nanozyme to treat ROS-related diseases.