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Highly efficient control of thrombin activity by multivalent nanoparticles.

Chia-Lun Hsu¹, Huan-Tsung Chang, Chao-Tsen Chen

¹Institute of Bioscience and Biotechnology and Center of Excellence for Marine Bioenvironment and Biotechnology, National Taiwan Ocean University, 2, Beining Road, Keelung, 20224, Taiwan.

Chemistry (Weinheim an Der Bergstrasse, Germany)

|August 19, 2011

Summary

This summary is machine-generated.

We developed novel gold nanoparticles conjugated with aptamers and sulfated galactose acid for effective blood clot inhibition. These multivalent nanoparticles show ultrahigh affinity for thrombin, significantly prolonging clotting time and offering potential for controlling coagulation.

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Area of Science:

Biomedical Engineering
Nanotechnology
Biochemistry

Background:

Thrombin plays a critical role in blood coagulation.
Developing effective inhibitors of thrombin activity is crucial for managing thrombotic disorders.
Aptamer-conjugated gold nanoparticles offer a promising platform for targeted drug delivery and therapeutic applications.

Purpose of the Study:

To investigate the efficacy of sulfated galactose acid (sulf-Gal)-modified thrombin-binding aptamer (TBA)-conjugated gold nanoparticles (AuNPs) in inhibiting thrombin activity.
To optimize the composition of TBA-AuNPs for enhanced anticoagulant potency.
To evaluate the potential of these nanoconjugates for biomedical control of blood clotting.

Main Methods:

Synthesis of gold nanoparticles (AuNPs) conjugated with 15-mer TBA (TBA(15)), 29-mer TBA (TBA(29)), and sulf-Gal.
Characterization of AuNP bioconjugates (TBA(15)/TBA(29)/sulf-Gal-AuNPs) and assessment of molecule density per AuNP.
Measurement of thrombin binding affinity (K(d)) and thrombin clotting time (TCT) to determine anticoagulant potency.
Evaluation of the suppression of anticoagulant activity using complementary TBA (cTBA)-modified AuNPs.

Main Results:

The optimal configuration, 15-TBA(15)/TBA(29)/sulf-Gal-AuNPs, exhibited an ultrahigh binding affinity for thrombin (K(d)=3.4×10(-12) M).
These optimized nanoconjugates significantly prolonged thrombin clotting time (91-fold increase) compared to controls.
Anticoagulant activity was effectively suppressed by cTBA-modified AuNPs, with faster kinetics than free cTBA.

Conclusions:

Multivalent AuNPs incorporating TBA and sulf-Gal are highly effective inhibitors of thrombin activity.
The density of TBA and sulf-Gal on AuNPs critically influences inhibitory potency.
These easily prepared, low-cost nanoconjugates demonstrate significant potential for the biomedical control of blood clotting.