Gold nanoparticles modified with self-assembled hybrid monolayer of triblock aptamers as a photoreversible anticoagulant
Journal
Journal of Controlled Release
Journal Volume
221
Pages
9-17
Date Issued
2016
Author(s)
Abstract
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 TBA15 (15-base, binding to the exosite I of thrombin) and TBA29 (29-base, binding to the exosite II of thrombin) provided bivalent interaction with thrombin. The SAHM triblock aptamers have optimal distances between TBA15 and TBA29, aptamer density, and orientation on the Au NP surfaces. These properties strengthen the interactions with thrombin (Kd = 1.5 × 10- 11 M), resulting in an extremely high anticoagulant potency. The thrombin clotting time mediated by SAHM TBA15/TBA29-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 SAHM TBA15/TBA29-Au NPs were superior to heparin. The SAHM TBA15/TBA29-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 SAHM TBA15/TBA29-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), low cost (non-thiolated aptamer), photo-controllable, multivalent TBA15/TBA29-Au NPs (high density of TBA15/TBA29 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. ? 2015 Elsevier B.V. All rights reserved.
Subjects
Anticoagulants; Aptamers; Gold nanoparticles; Self-assemble; Thrombin
SDGs
Other Subjects
Bins; Biocompatibility; Drug products; Enzyme activity; Enzymes; Fiber optic sensors; Gold alloys; Heat transfer; Metal nanoparticles; Monolayers; Nanoparticles; Oligonucleotides; Plasma stability; Polysaccharides; Self assembly; Anticoagulants; Aptamers; Gold Nanoparticles; Self-assemble; Thrombin; Gold; 15 mer thrombin binding aptamer; 29 mer thrombin binding aptamer; anticoagulant agent; aptamer; argatroban; fibrinogen; gold nanoparticle; heparin; hirudin; oligonucleotide; self assembled monolayer; thrombin; unclassified drug; warfarin; anticoagulant agent; aptamer; delayed release formulation; gold; metal nanoparticle; thrombin; thrombin aptamer; adult; animal experiment; animal model; anticoagulation; antineoplastic activity; Article; binding affinity; biocompatibility; bleeding time; blood clotting disorder; blood clotting time; chemical interaction; clinical effectiveness; clinical evaluation; cytotoxicity; drug conjugation; drug half life; drug potency; drug release; drug structure; enzyme activity; enzyme inhibition; heat transfer; hemolysis; human; human cell; human experiment; hybridization; irradiation; male; nonhuman; normal human; priority journal; rat; structure analysis; surface property; systematic review; thrombin time; young adult; animal; chemistry; delayed release formulation; light; metabolism; Sprague Dawley rat; Animals; Anticoagulants; Aptamers, Nucleotide; Delayed-Action Preparations; Fibrinogen; Gold; Humans; Light; Male; Metal Nanoparticles; Rats; Rats, Sprague-Dawley; Thrombin
Type
journal article