Design and characterization of antithrombotic ClEKnsTy-Au nanoparticles as diagnostic and therapeutic reagents.

Abstract

Thrombosis can cause various cardiovascular diseases, which seriously endanger human life. Development of diagnostic and therapeutic reagents for thrombosis at an early stage would be helpful for the improvement of treatment and the reduction of mortality. In the present study, based on an antithrombotic peptide lEKnsTy (lowercase letters represent D-amino acid residues), a diagnostic and therapeutic reagent targeting collagen and the early stage of thrombosis was proposed, where cysteine was introduced into the amino terminus of lEKnsTy to prepare ClEKnsTy, followed by coupling with AuNPs to prepare nanoconjugate AuNP-Cl. The binding of AuNP-Cl on the collagen surface was then confirmed by the molecular dynamics simulations of the binding of ClEKnsTy on collagen, and the experimental results of the binding of AuNP-Cl on collagen. The inhibition of platelet adhesion on the collagen surface by AuNP-Cl was also confirmed. Moreover, the good imaging ability of AuNP-Cl was confirmed by dark-field microscopy. These results indicated that AuNP-Cl was a potential effective diagnostic and therapeutic reagent targeting collagen, which would be helpful for the research and development of multifunctional antithrombotic reagents.