Highly Efficient Control of Thrombin Activity by Multivalent Nanoparticles
Journal
Chemistry - A European Journal
Journal Volume
17
Journal Issue
39
Pages
10994-11000
Date Issued
2011
Author(s)
Abstract
We have demonstrated that the incorporation of sulfated galactose acid (sulf-Gal) into thrombin-binding-aptamer (TBA)-conjugated gold nanoparticles (TBA-AuNPs) enables highly effective inhibition of thrombin activity toward fibrinogen. AuNP bioconjugates (TBA 15/TBA 29/sulf-Gal- AuNPs) were prepared from 13 nm AuNPs, 15-mer thrombin-binding aptamer (TBA 15), 29-mer thrombin-binding aptamer (TBA 29), and sulf-Gal. The numbers of TBA and sulf-Gal molecules per AuNP proved to have a strong impact on inhibitory potency. The best results were observed for 15-TBA 15/TBA 29/sulf-Gal-AuNPs (with 15 TBA 15 and 15 TBA 29 molecules per AuNP), which, because of their particularly flexible conformation and multivalency, exhibited ultrahigh binding affinity toward thrombin (K d=3.4Ã-10 -12 M) and thus extremely high anticoagulant (inhibitory) potency. Compared to the case without inhibitors (the "normal" value), their measured thrombin clotting time (TCT) was 91 times longer, whereas for TBA 15 alone it was only 7.2 times longer. Their anticoagulant activity was suppressed by TBA-complementary-sequence (cTBA)-modified AuNPs (cTBA 15/cTBA 29-AuNPs) at a rate that was 20 times faster than that of free cTBA 15/cTBA 29. Thus, easily prepared, low-cost, multivalent AuNPs show great potential for biomedical control of blood clotting. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
SDGs
Type
journal article