STING antagonist-loaded renal tubule epithelial cell-mimicking nanoparticles ameliorate acute kidney injury by orchestrating innate and adaptive immunity

Inflammatory responses profoundly contribute to the development of renal damage in acute kidney injury (AKI), a frequent clinical syndrome with high morbidity and mortality. However, the effects of existing strategies aiming to suppress the inflammation in AKI remain unsatisfactory due to the inability to simultaneously regulate innate and adaptive immune responses. Here, STING antagonist -loaded renal tubule epithelial cell membranecoated nanoparticles (SNP@TEC) are developed to ameliorate AKI by orchestrating innate and adaptive immunity. As the reservation of cell membrane alpha V integrin, biomimetic SNP@TEC are able to target renal tubules via homotypic tropism. The carried antagonist can suppress innate immune responses through relieving STINGtriggered inflammatory reaction and repolarizing macrophages to the anti-inflammatory M2 phenotype. Owing to the presence of cell membrane PD -L1, SNP@TEC can also elicit an anti-inflammatory adaptive immune response by blocking the CD80 on dendritic cells to inhibit T -cell activation. In two murine models of AKI induced by cisplatin or ischemia/reperfusion, systemic injection with SNP@TEC significantly alleviates renal damage and restores renal function. In a prophylactic model, SNP@TEC effectively prevent the transition of AKI to chronic kidney disease. SNP@TEC propose a unique approach to orchestrate innate and adaptive immunity, opening a window to remit inflammation for treating renal injury.