A novel biomimetic approach for direct delivery of clot-dissolving nanotherapeutics to the site of obstructed blood vessels has been devised by researchers from Harvard University’s Wyss Institute for Biologically Inspired Engineering.
Nanotherapeutic administered directly to the clot site (Credit: Wyss Institute for Biologically Inspired Engineering, Harvard)
Use of currently available clot-busting drugs is often accompanied by profuse bleeding, thereby limiting widespread prescription of these drugs. The new strategy overcomes this limitation by facilitating the dissolution of the clot by utilizing just a fraction of the normally required drug dosage.
Severe vascular blockage by blood clots results in stroke, heart attack and pulmonary embolism. These are some of the major causes of death and the study findings will significantly impact the treatment of these life-threatening conditions. The researchers took inspiration from biology for shaping their strategy. When blood vessels in the body constrict, the resulting high shear stresses serve as a signal to the circulating platelets to selectively adhere to the walls of the blood vessels, leading to the formation of atherosclerotic plaques. The vascular nanotherapeutic is the same size as platelets and is made up of biodegradable nanoparticles coated with the clot-dissolving drug, tissue plasminogen activator (tPA). On sensing shear stress as a result of blood clot induced vascular constriction, the tPA nanoparticles selectively dissociate from the aggregate and attach themselves to clots to wear them down. Life threatening conditions such as heart attacks, strokes and pulmonary embolism that are brought about by acute thrombosis are usually treated in intensive care hospital settings with regular dosages of clot-dissolving drugs. The fatal bleeding that accompanies the increased usage of these drugs limits the size of dosage administered. The new nanotherapeutic method overcomes the efficacy limitations. The research team demonstrated improved survival in mice with obstructed lung vessels by administering less than 1/50th of the normal dosage via the new method. This opens up future possibilities where emergency personnel can administer the life-saving drug themselves even before the patient is taken to the hospital.