Self-assembled, bivalent aptamers on graphene oxide as an efficient anticoagulant
Journal
Biomaterials Science
Date Issued
2018
Author(s)
Abstract
Graphene oxide (GO) has unique structural properties, can effectively adsorb single-strand DNA through π-π stacking, hydrogen bonding and hydrophobic interactions, and is useful in many biotechnology applications. In this study, we developed a thrombin-binding-aptamers (15- and 29-mer) conjugated graphene oxide (TBA 15 /TBA 29 -GO) composite for the efficient inhibition of thrombin activity towards the formation of fibrin from fibrinogen. The TBA 15 /TBA 29 -GO composite was simply obtained by the self-assembly of TBA 15 /TBA 29 hybrids on GO. The high density and appropriate orientation of TBA 15 /TBA 29 on the GO surface enabled TBA 15 /TBA 29 -GO to acquire an ultrastrong binding affinity for thrombin (dissociation constant = 2.9 × 10 -12 M). Compared to bivalent TBA 15 h 20 A 20 /TBA 29 h 20 A 20 hybrids, the TBA 15 /TBA 29 -GO composite exhibited a superior anticoagulant potency (ca. 10-fold) against thrombin-mediated coagulation as a result of steric blocking effects and a higher binding affinity for thrombin. In addition, the prolonged thrombin clotting time, prothrombin time (PT), and activated partial thromboplastin time (aPTT) of TBA 15 /TBA 29 -GO were at least 2 times longer than those of commercially available drugs (heparin, argatroban, hirudin, and warfarin). The in vitro cytotoxicity and hemolysis analyses revealed the high biocompatibility of TBA 15 /TBA 29 -GO. The rat-tail bleeding assay of the hemostasis time and ex vivo PT and aPTT further revealed that TBA 15 /TBA 29 -GO is superior (>2-fold) to heparin, which is commonly used in the treatment and prevention of thrombotic diseases. Our multivalent, oligonucleotide-modified GO nanocomposites are easy to prepare, cost-effective, and highly biocompatible and they show great potential as effective anticoagulants for the treatment of thrombotic disorders. ? The Royal Society of Chemistry.
SDGs
Other Subjects
Binding energy; Biocompatibility; Cost effectiveness; Dissociation; Drug products; Enzymes; Hydrogen bonds; Hydrophobicity; Oligonucleotides; Polysaccharides; Self assembly; Activated partial thromboplastin time; Binding affinities; Biotechnology applications; Dissociation constant; Hydrophobic interactions; Prothrombin time; Single strand DNA; Thrombotic disorders; Graphene; anticoagulant agent; aptamer; argatroban; fibrin; fibrinogen; graphene oxide; hirudin; nanocomposite; thrombin; thrombin inhibitor; warfarin; anticoagulant agent; aptamer; graphite; heparin; hirudin derivative; oxide; pipecolic acid derivative; protein binding; single stranded DNA; thrombin; activated partial thromboplastin time; animal experiment; animal model; anticoagulation; Article; binding affinity; biocompatibility; bleeding; controlled study; density; dissociation constant; drug conjugation; drug cytotoxicity; drug potency; ex vivo study; hemolysis assay; hemostasis; human; human cell; in vitro study; male; nonhuman; priority journal; prothrombin time; rat; surface property; thrombin time; thromboelastography; adsorption; animal; antagonists and inhibitors; binding competition; blood clotting; chemical phenomena; chemistry; drug effect; hydrogen bond; metabolism; Sprague Dawley rat; synthesis; Adsorption; Animals; Anticoagulants; Aptamers, Nucleotide; Binding, Competitive; Blood Coagulation; DNA, Single-Stranded; Graphite; Heparin; Hirudins; Humans; Hydrogen Bonding; Hydrophobic and Hydrophilic Interactions; Male; Oxides; Pipecolic Acids; Protein Binding; Rats; Rats, Sprague-Dawley; Thrombin
Type
journal article