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

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 P2Y₁₂-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.