Atherosclerosis, a silent disease, becomes life-threatening when atherosclerotic plaque ruptures, leading to the formation of thrombus, and acute and severe cardiovascular events. The injection of recombinant tissue plasminogen activator (rt-PA) is the only recommended treatment in ischemic stroke in France. However, due to the risks of serious complications, less than 10% of patients receive the treatment. There is an unmet medical need for nanomedicine-based safe thrombus targeting thrombolytic therapy.
In my PhD project, polysaccharide nanoparticles, as a drug carrier, are elaborated by a green chemistry method using natural compounds. A safer non-neurotoxic mutant of the original rt-PA will be loaded on the nanoparticles beforehand functionalized with a thrombus targeted agent (fucoidan). Safety and efficacy of the developed system will be assessed in in vitro and in vivo animal models of thrombosis.
In conclusion, my project deals with a safer targeted thrombolytic therapy due to the application of the nanomedicine, use of natural resources, and green chemistry processes.