Aptamer‐Conjugated Nanoparticles Efficiently Control the Activity of Thrombin

Abstract

Abstract Thrombin‐binding aptamer‐conjugated gold nanoparticles (TBA‐Au NPs) for highly effective control of thrombin activity towards fibrinogen are demonstrated. While a 29‐base long oligonucleotide (TBA 29 ) has known no enzymatic inhibitory functions for thrombin‐mediated coagulation, the ultrahigh anticoagulant potency of TBA 29 ‐Au NPs can be demonstrated via the steric blocking effect, at two orders of magnitude higher than that of free TBA 29 . The surface aptamer density on the Au NPs is important in determining their enzymatic inhibition of thrombin and their stability in the presence of nuclease. The practicality of 100TBA 29 ‐Au NPs (100 TBA 29 molecules per Au NP) for controlling thrombin‐mediated coagulation in plasma is found, and the 100TBA 29 ‐Au NPs has an ultra binding affinity towards thrombin ( K d = 2.7 × 10 −11 M ) due to their high ligand density. The anticoagulant activity of TBA 29 ‐Au NPs is found to be suppressed by TBA 29 complementary sequence (cTBA 29 ) modified Au NPs (cTBA 29 ‐Au NPs), with a suppression rate 4.6‐fold higher than that of cTBA 29 . The easily prepared and low‐cost TBA 29 ‐Au NPs and cTBA 29 ‐Au NPs show their potential in biomedical applications for treating various diseases related to blood clotting disorders. In principle, this study opens the possibility of regulation of molecule binding, protein recognizing, and enzyme activity by using aptamer‐functionalized nanomaterials.