Figure 1.

Platelet-mediated hemostatic mechanism and platelet-inspired t-TLNP design. (A) Platelets rapidly adhere at a vascular injury site by binding to von Willebrand factor (vWF, via platelet surface GPIbα) and collagen (via platelet surface GPIa/IIa and GPVI) exposed at the site and present high amounts of an anionic phospholipid such as phosphatidylserine (PS) on the activated platelet procoagulant membrane surface to enable the assembly of coagulation factors to form tenase (FVIIa + FIXa + FX) and prothrombinase (FXa + FVa + FII) complexes, ultimately leading to the amplified generation of thrombin (thrombin burst); the thrombin locally converts fibrinogen (Fg) to fibrin that gets cross-linked by FXIIIa for hemostatic clot formation. (B) t-TLNPs can undergo platelet-mimetic adhesion at the vascular injury site by anchoring to vWF via vWF-binding peptide (VBP) and collagen via collagen-binding peptide (CBP) and release thrombin at the site via diffusion as well as injury site secreted phospholipase A₂ (sPLA₂) triggered particle destabilization; this thrombin can locally convert fibrinogen (Fg) to fibrin for hemostatic action.