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

Abstract

ABSTRACT cis ‐Diols play critical roles in biological systems and form key structural motifs in many pharmaceuticals and vaccines. Specific in vivo recognition of a bioactive cis ‐diol and subsequent functional manipulation is thus desirable but remains challenging. Here, we present a boronic acid–functionalized gold nanoparticle (AuNP) platform that accomplishes this goal by uncovering the exceptional capacity of o ‐carborane decorated boronic acid to disrupt P2Y 12 ‐Ticagrelor binding and by highlighting the dual stabilizing roles of o ‐carboranyl via carbon ligation and B–H···Au chemisorption. Furthermore, by exploiting carborane‐derived counterions, we introduce a counterion‐engineering strategy that decouples water solubility from the chemical vulnerability of boronic acid. The resulting intravenous nanosystem selectively neutralizes Ticagrelor, a cis ‐diol–containing antiplatelet drug, with high efficacy demonstrated in both mouse and pig bleeding models. This work establishes the first chemical strategy for in vivo Ticagrelor reversal and offers a broadly applicable framework for diol targeting and nanomaterial design in complex biological environments.