Design of a Novel, Dual-Functioning, Tissue Plasminogen Activator and Factor XI Inhibiting Anticoagulant Therapeutic for Rapid Ischemic Stroke Treatment

Overview

Stroke is the second leading cause of death worldwide, with 15 million people suffering from its debilitating effects each year. 87% of strokes are ischemic, where an artery narrows or becomes wholly blocked due to a thrombus. Tissue Plasminogen Activator (tPA) is a protein that activates the conversion of plasminogen to plasmin, an enzyme responsible for the breakdown of clots. While tPA is the leading emergency treatment for ischemic stroke, it possesses several shortcomings, including a non-localized nature and increased risk of hemorrhage. Similarly, no existing therapeutic candidates have dissolved the thrombus and simultaneously deterred the coagulation cascade, the process by which a thrombus is actively built. Herein, a rapid, clot-specific, and dual-functioning microbubble system utilizing tPA and a Factor XI inhibiting polyclonal antibody was engineered to create a more effective emergency therapeutic. T o begin, fabrication of the magnetic interior nanoparticles was completed by synthesizing Dicumarol-Carboxylic-acid coated Fe3O4 nanoparticles in the first iteration of the interior structure. Next, SiO2-tPA was fabricated and added to complete the subsequent encapsulation layer of the nanoparticles. After sonication and synthesis of a “microbubble” structure, peptides CGSSSGRGDSPA and GRGD were conjugated to the exterior to promote selectivity for platelets and fibrin and ensure clot-specific adhesion and release. A vertical gel channel system, composed of fibrinogen, thrombin, and agarose, was developed to validate the clot dissolution as a function of the new therapeutic, which was 2x that of tPA alone. As a final verification component, in-vitro clots were created using ~100µl of whole-blood in a 96-wellplate.

Competition history

• JSHS 2023 Category not listed

Resources

• National JSHS abstract book ↗

Related projects

Closest projects by meaning, across every fair and year in the corpus.