Abstract 1943: Potential of Fibrin-Targeted Streptokinase-Activated Nanoparticles for Early Revascularization in Acute Ischemic Stroke
A safe and effective fibrinolytic agent that can be given upon presentation of acute ischemic stroke with few exclusionary criteria is needed.
Objective: Develop a vascular constrained, fibrin-targeted thrombolytic perfluorocarbon nanoparticle (~240nm) that is surface modified to deliver effective fibrinolytic therapy at lower doses than current thrombolytic strategies.
Methods: In a series of in vitro experiments, human plasma clots (n=4 to 7/group) were targeted with streptokinase-nanoparticles, control nanoparticles, or a mixture of both vitro. Clots were exposed to phosphate buffered saline (PBS), PBS with plasminogen, or PBS with plasminogen and free streptokinase, and lysis was monitored at 15-minute intervals with quantitative ultrasound.
Results: Targeted streptokinase-nanoparticles induced rapid fibrinolysis (> 90% in 60 minutes p<0.05) without concurrent microbubble production, rupture or cavitation. Control or streptokinase-nanoparticles in PBS alone did not induce clot lysis. Effective concentrations of targeted streptokinase were several orders of magnitude lower than equivalently efficacious levels of free enzyme. Competitive inhibition of fibrin-bound streptokinase nanoparticles reduced clot lysis monotonically. As little as 1% surface targeting produced decreases (p<0.05) in clot volumes (~30%).
Conclusion: This study demonstrates the concept of a novel, targeted nanoparticle-based thrombolytic agent that will be vascularly constrained and produce provide rapid fibrinolysis with markedly lower dosages of enzyme, potentially shortening the time to reperfusion for stroke victims.