Direct delivery of plasmin using clot-anchoring thrombin-responsive nanoparticles for targeted fibrinolytic therapy.

ABSTRACT:

Background

Fibrin-rich clot formation in thrombo-occlusive pathologies is currently treated by systemic administration of plasminogen activators (e.g. tPA), to convert fibrin-associated plasminogen to plasmin for fibrinolytic action. However, this conversion is not restricted to clot site only but also occurs on circulating plasminogen, causing systemic fibrinogenolysis and bleeding risks. To address this, past research has explored tPA delivery using clot-targeted nanoparticles.

Objectives

We designed a nanomedicine system that can (1) target clots via binding to activated platelets and fibrin, (2) package plasmin instead of tPA as a direct fibrinolytic agent, and (3) release this plasmin triggered by thrombin for clot-localized action.

Methods

Clot-targeted thrombin

SUBMITTER: Sun M 

PROVIDER: S-EPMC10148984 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature