Thrombin-inhibiting perfluorocarbon nanoparticles provide a novel strategy for the treatment and magnetic resonance imaging of acute thrombosis.

ABSTRACT:

Background

As a regulator of the penultimate step in the coagulation cascade, thrombin represents a principal target of direct and specific anticoagulants.

Objective

A potent thrombin inhibitor complexed with a colloidal nanoparticle was devised as a first-in-class anticoagulant with prolonged and highly localized therapeutic impact conferred by its multivalent thrombin-absorbing particle surface.

Methods

PPACK (Phe[D]-Pro-Arg-Chloromethylketone) was secured covalently to the surface of perfluorocarbon-core nanoparticle structures. PPACK and PPACK nanoparticle inhibition of thrombin were assessed in vitro via thrombin activity against a chromogenic substrate. In vivo antithrombotic activity of PPACK, heparin, non-functionalized nanoparticles and PPACK nanoparticles wa

SUBMITTER: Myerson J 

PROVIDER: S-EPMC3686484 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature