Counterion-Engineered Water-Stable Intravenously Administered Nanoparticles Enable In Vivo Reversal of Ticagrelor

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Medicinal Chemistry

Background:

• Cis-diols are crucial in biological systems and drug structures.
• Targeting bioactive cis-diols in vivo is challenging.
• Ticagrelor is an antiplatelet drug containing a cis-diol.

Purpose of the Study:

• To develop a platform for in vivo recognition and functional manipulation of cis-diols.
• To create a method for reversing Ticagrelor's antiplatelet activity.
• To design a nanomaterial for targeted drug neutralization.

Main Methods:

• Functionalization of gold nanoparticles (AuNPs) with boronic acid and o-carborane.
• Utilizing o-carborane's ability to disrupt P2Y12-Ticagrelor binding.
• Employing carborane-derived counterions for enhanced solubility and stability.
• Developing an intravenous nanosystem for drug neutralization.

Main Results:

• The boronic acid-functionalized AuNP platform selectively targets and neutralizes Ticagrelor.
• The o-carborane decoration enhances binding disruption and nanoparticle stability.
• Counterion engineering improved water solubility while maintaining boronic acid integrity.
• High efficacy in reversing Ticagrelor's effects was demonstrated in mouse and pig bleeding models.

Conclusions:

• This study presents the first chemical strategy for in vivo Ticagrelor reversal.
• The developed nanosystem offers a new approach for managing antiplatelet drug activity.
• The platform provides a broadly applicable framework for cis-diol targeting and nanomaterial design in biological settings.