Tetrahedral framework nucleic acid nanomaterials reduce the inflammatory damage in sepsis by inhibiting pyroptosis

Abstract

Sepsis is a highly lethal condition and is caused by the dysregulation of the body's immune response to infection. Indeed, sepsis remains the leading cause of death in severely ill patients, and currently, no effective treatment is available. Pyroptosis, which is mainly activated by cytoplasmic danger signals and eventually promote the release of the pro-inflammatory factors, is a newly discovered programmed cell death procedure that clears infected cells while simultaneously triggering an inflammatory response. Increasing evidence indicates that pyroptosis participates in the development of sepsis. As a novel DNA nanomaterial, tetrahedral framework nucleic acids (tFNAs) characterized by its unique spatial structure, possess an excellent biosafety profile and can quickly enter the cell to impart anti-inflammatory and anti-oxidation effects. In this study, the roles of tFNAs in the in vitro model of macrophage cell pyroptosis and in the in vivo model of septic mice were examined, and it was found that tFNAs could mitigate organ inflammatory damage in septic mice, wherein they reduced inflammatory factor levels by inhibiting pyroptosis. These results provide possible new strategies for the future treatment of sepsis.