Artificial platelets suppressing deep vein thrombosis via competitive adhesion.

Deep vein thrombosis (DVT) remains a therapeutic challenge, primarily driven by pathological platelet adhesion at sites of vascular injury mediated by endothelial adhesion molecule overexpression. However, the molecular mechanisms underlying endothelial-dependent pathological platelet adhesion remain elusive. Here, integrating single-cell RNA sequencing (scRNA-seq) and functional validation, we identified aberrant activation of the stimulator of interferon genes (STING) as a critical driver of endothelial dysfunction and pathological platelet adhesion. Using STING knockout mice, we confirmed its central role in promoting a prothrombotic microenvironment via the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome. Targeting this pathway, we identified forsythoside A (FA) as a potent STING inhibitor and constructed artificial platelets (Pm@Fng) via photopolymerization-membrane extrusion technology. Pm@Fng, consisting of FA-loaded nanogels cloaked with activated platelet membrane vesicles (APMVs), exhibited enhanced glycoprotein Ib alpha (GPIbα) -mediated binding affinity to von Willebrand factor (vWF), competitively blocking pathological platelet adhesion. Under thrombotic microenvironment (acidic pH and high reactive oxygen species), FA was released to modulate the STING - NLRP3 pathway, suppressing adhesion molecule expression. In a mouse DVT model, Pm@Fng rapidly targeted the endothelium, noticeably reducing thrombosis by 30% (p < 0.001) and preserving endothelial integrity. By exploiting competitive adhesion principles, this study presents a novel therapeutic strategy for DVT and other endothelial injury-related diseases.