Micellar Thrombin-Binding Aptamers: Reversible Nanoscale Anticoagulants

Area of Science:

• Biochemistry
• Nanotechnology
• Biomedical Engineering

Background:

• Aptamers are nucleic acid ligands with specific binding capabilities.
• Aptamers show potential as anticoagulants by targeting coagulation cascade enzymes.
• Free aptamers face challenges like nuclease degradation and rapid clearance.

Purpose of the Study:

• To develop stabilized aptamer-based anticoagulants.
• To improve the pharmacokinetic properties of aptamers for in vivo applications.
• To create aptamer-drug conjugates that self-assemble into functional nanostructures.

Main Methods:

• Synthesis of thrombin-binding aptamer amphiphiles.
• Self-assembly of amphiphiles into nanoscale polymeric micelles.
• Assessment of micellar aptamer structure, stability, and anticoagulant activity in vitro and in vivo.

Main Results:

• Micellar aptamers retained native secondary structure in crowded environments.
• Aptamer micelles demonstrated enhanced stability against nucleases in human serum.
• Effective inhibition of human plasma clotting in vitro with rapid reversal via hybridization.
• Increased molecular weight and size of micellar aptamers led to extended blood circulation times in vivo.

Conclusions:

• Aptamer amphiphiles self-assemble into stabilized, functional nanostructures.
• Micellar aptamers overcome limitations of free aptamers, showing improved stability and pharmacokinetics.
• This platform offers a promising strategy for developing advanced aptamer-based therapeutics, including anticoagulants.