Gold nanoparticles modified with self-assembled hybrid monolayer of triblock aptamers as a photoreversible anticoagulant

We demonstrated that thrombin-binding aptamer-conjugated gold nanoparticles (TBA-Au NPs), prepared from a self-assembled hybrid monolayer (SAHM) of triblock aptamers on Au NPs (13 nm), can effectively inhibit thrombin activity toward fibrinogen. The first block poly(adenine) at the end of the triblock TBA was used for the self-assembly on Au NP surface. The second block, in the middle of TBA, was composed of oligonucleotides that could hybridize with each other. The third block, containing TBA(15) (15-base, binding to the exosite I of thrombin) and TBA(29) (29-base, binding to the exosite II of thrombin) provided bivalent interaction with thrombin. The SAHM triblock aptamers have optimal distances between TBA(15) and TBA(29), aptamer density, and orientation on the Au NP surfaces. These properties strengthen the interactions with thrombin (K-d = 1.5 x 10(-11) M), resulting in an extremely high anticoagulant potency. The thrombin clotting time mediated by SAHM TBA(15)/TBA(29)-Au NPs was >10 times longer than that of four commercially available drugs (heparin, argatroban, hirudin, or warfarin). In addition, the rat-tail bleeding assay time further demonstrated that the SAHMTBA(15)/TBA(29)-Au NPswere superior to heparin. The SAHMTBA(15)/TBA(29)-Au NPs exhibited excellent stability in the human plasma (half-life > 14 days) and good biocompatibility (low cytotoxicity and hemolysis). Most interestingly, the inhibition by SAHMTBA(15)/TBA(29)-Au NPs was controllable by the irradiation of green laser, via heat transfer-induced TBA release from Au NPs. Therefore, these easily prepared (self-assembled), lowcost (non-thiolated aptamer), photo-controllable, multivalent TBA(15)/TBA(29)-Au NPs (high density of TBA(15)/TBA(29) on Au NPs) show good potential for the treatment of various diseases related to blood-clotting disorders. Our study opens up the possibility of regulation of molecule binding, protein recognition, and enzyme activity using SAHM aptamer-functionalized nanomaterials. (C) 2015 Elsevier B.V. All rights reserved.