- Oral presentation
- Open Access
Thrombin inhibitor perfluorocarbon nanoparticles for treatment and 19F tracking of acute thrombosis
© Myerson et al; licensee BioMed Central Ltd. 2010
- Published: 21 January 2010
- Carotid Artery
- Acute Thrombosis
- Thrombin Cleavage
- Injured Artery
Localized thrombus formation as a consequence of cardiovascular disorders can lead to acute arterial or venous occlusions. Heparin is the standard medication in emergency treatment of occlusive events, but optimization of antithrombotic mediation of acute thrombi remains a significant research challenge.
Perfluorocarbon (PFC) nanoparticles (NPs) were functionalized via covalent attachment of the irreversible thrombin inhibitor, PPACK (Phe(D)-Pro-Arg-Chloromethylketone). Particle-PPACK coupling was verified through zeta potential measurement and HPLC quantification. Inhibition of thrombin cleavage of Tosyl-Gly-Pro-Arg-4 nitranilide acetate was assessed via optical assay to verify that PPACK activity against thrombin and selectivity for thrombin over plasmin was not diminished on attachment to the particles. PPACK NPs (n = 7), PPACK (n = 4), heparin (n = 4), non-functionalized NPs (n = 7), and saline (n = 7) were used to treat C57BL6 mice immediately following laser injury of the carotid artery. Time to thrombotic occlusion of the injured artery was assessed via Doppler flow measurement. For selected mice receiving NPs, particle retention in extracted carotid arteries was assessed via 19F MRS/MRI at 11.7 T.
In our model, PPACK-functionalized PFC NPs surpassed heparin in treatment of acute thrombosis. The particles take advantage of PPACK's high affinity and specificity for thrombin while utilizing the vascular confinement and long circulating half-life of the PFC NPs. 19F MRS and MRI indicate that PPACK NPs are retained in forming clots. As a potent antithrombotic that can be traced with 19F MRS and MRI, PPACK NPs have great therapeutic potential.
This article is published under license to BioMed Central Ltd.