Harnessing micrometer-scale tPA beads for high plasmin generation and accelerated fibrinolysis.

ABSTRACT: Rapid restoration of blood flow is critical in treating acute ischemic stroke. Current fibrinolytic therapies using tissue plasminogen activator (tPA) are limited by low recanalization rates and risks of off-target bleeding. Here, we present a strategy using tPA immobilized on micrometer-scale beads to enhance local plasmin generation. We synthesized tPA-functionalized beads of varying sizes (0.1 μm and 1.0 μm) and evaluated their efficacy. In vitro assays demonstrated that 1.0 μm tPA-beads generated higher plasmin generation compared to free tPA and 0.1 μm beads, overcoming antiplasmin inhibition and promoting a self-propagating wave of fibrinolysis. In a murine model of acute ischemic stroke, intravenous administration of 1.0 μm tPA-beads at doses nearly two orders of magnitude lo

SUBMITTER: Osmond MJ 

PROVIDER: S-EPMC11580863 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature