Targeted Drug Delivery to Endothelial Adhesion Molecules

Figure 8

“On demand” fibrinolysis by vascular targeting of thrombin-activated anti-PECAM scFv/uPA (scFv/uPA-T). scFv-uPA/T circulates in a prodrug form, single-chain uPA (scuPA), binds to PECAM-1 and remains anchored on the endothelial luminal surface for at least several hours. Upon environmental stress or tissue injury, thrombin is generated to cleave fibrinogen (Fg) and form fibrin clots. While this causes in situ thrombosis, the generated thrombin also converts the endothelium-bound scFv/uPA-T to enzymatically active tcuPA, inducing local conversion of plasminogen (Pg) into plasmin (Pn). The active plasmin subsequently facilitates fibrinolysis that restores the blood flow and mitigates the tissue ischemia and injury. From Simone et al. [322].