Spatially selective clearance of inflammation-mediated reactive oxygen species in injured kidney cells

<b>Rationale:</b> Kidney injury is characterized by the accumulation of reactive oxygen species (ROS). Current ROS scavengers utilized in the treatment of clinical kidney injury lack the capacity for spatially selective ROS scavenging within the injured cells, often resulting in irreversible damage to healthy tissues. <b>Methods:</b> We developed a spatially selective therapeutic strategy using platelet-shipped tetrahedral framework nucleic acids (TFNAs@PLT). <b>Results:</b> In this system, platelets achieve spatial targeting of injured kidney cells by responding to inflammatory signals and releasing TFNAs following TNF-α activation. TFNAs subsequently exert a potent antioxidant effect in the injured cells. We have demonstrated that TFNAs@PLT reduces pyroptosis and apoptosis through the Caspase-3/GSDME pathway and the NLRP3-mediated Caspase-1/IL-1β pathway in the acute kidney injury (AKI) mouse model, while also inhibiting renal fibrosis <i>via</i> the NLRP3/Caspase-1 and the TNF-α/NF-κB pathways in the chronic kidney disease (CKD) mouse model. <b>Conclusion:</b> TFNAs@PLT offers a safe and effective therapeutic strategy for kidney injury and other inflammation-mediated diseases.