Multifunctional Selenium-Based Metal Polyphenol Nanoparticles Impede the Pathological Cross-talk Between Reactive Oxygen Species and Inflammation in Sepsis

Oxidative stress and dysregulated inflammation lead to a detrimental loop in sepsis, which results in cytokine storms and multiorgan failure. Development of a high-performance nanozyme to impede the pathological cross-talk is an effective strategy. Herein, we develop multifunctional tannic acid-Zn-coated selenium nanoparticles (TZn@CSe) with superoxide dismutase and glutathione peroxidase-like enzyme activities, which can effectively neutralize various types of ROS and decrease the expression of iNOS. Furthermore, they reversed the polarization of M1 macrophages and reduced the expression of inflammatory cytokines. Mechanistic assays revealed that TZn@CSe significantly modulated oxidative stress and inflammatory response signaling pathways, thereby alleviating cytokine storms. Eventually, TZn@CSe increased the survival rate of septic mice by 50% and ameliorated damage to the lungs, and the therapeutic efficacy of TZn@CSe surpassed that of the first-line clinical drug. Our work provides a feasible therapeutic method for alleviating sepsis to intercept the pathological interplay between ROS and inflammation.