Multienzyme Active Nanozyme for Efficient Sepsis Therapy through Modulating Immune and Inflammation Inhibition
Xin Qi, Shaofang Zhang, Si Sun, Nan Song, Yadong Zhe, Fangzhen Tian, Shu Zhang, Meili Guo, Xiaodong Zhang, Jianning Zhang, Hao Wang, Ruiping Zhang
Abstract
Sepsis, a life-threatening condition caused by a dysregulated immune response to infection, leads to systemic inflammation, immune dysfunction, and multiorgan damage. Various oxidoreductases play a very important role in balancing oxidative stress and modulating the immune response, but they are stored inconveniently, environmentally unstable, and expensive. Herein, we develop multifunctional artificial enzymes, CeO 2 and Au/CeO 2 nanozymes, exhibiting five distinct enzyme-like activities, namely, superoxide dismutase, catalase, glutathione peroxidase, peroxidase, and oxidase. These artificial enzymes have been used for the biocatalytic treatment of sepsis via inhibiting inflammation and modulating immune responses. These nanozymes significantly reduce reactive oxygen species and proinflammatory cytokines, achieving multiorgan protection. Notably, CeO 2 and Au/CeO 2 nanozymes with enzyme-mimicking activities can be particularly effective in restoring immunosuppression and maintaining homeostasis. The redox nanozyme offers a promising dual-protective strategy against sepsis-induced inflammation and organ dysfunction, paving the way for biocatalytic-based immunotherapies for sepsis and related inflammatory diseases.