Shear-Activated Nanotherapeutics for Drug Targeting to Obstructed Blood Vessels
Obstruction of critical blood vessels due to thrombosis or embolism is a leading cause of death world-wide. Here, we describe a biomimetic strategy that uses high shear stress caused by vascular narrowing as a targeting mechanism – in the same way platelets do–to deliver drugs to obstructed blood vessels. Microscale aggregates of nanoparticles were fabricated to break up into nanoscale components when exposed to abnormally high fluid shear stress. When coated with tissue plasminogen activator and administered intravenously in mice, these shear-activated nanotherapeutics induce rapid clot dissolution in a mesenteric injury model, restore normal flow dynamics, and increase survival in an otherwise fatal mouse pulmonary embolism model. This biophysical strategy for drug targeting, which lowers required doses and minimizes side effects while maximizing drug efficacy, offers a potential new approach for treatment of life-threatening diseases that result from acute vascular occlusion.
Brilliant research that is still in the animal research stages but could move on to human studies. Remember the patient in Costa Rica whose stent had clotted who passed away from internal bleeding due to a clot-busting drug. tPA that is in these nanoparticles is a clot-busting drug. If it can be delivered directly to the clot by the nanoparticles that target the high shear stress, this could prevent internal bleeding such as that which led to the Canadian patient's death. CCSVI IRs are not using tPA to treat clots in jugular veins most likely because of risks such as these; instead they are conservatively monitoring the clot while placing the patient on anticoagulants to prevent the clot from worsening or they are attempting manual clot removal which requires a repeat catheter venogram procedure. If something like these nanoparticles can make it to market, this would open up another way to treat clots. CCSVI IRs are also attempting to prevent clots by prescribing anticoagulation such as Pradaxa.