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March 13, 2026Angewandte Chemie0 citations

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

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WYWenchuang YangYTYabing TanJZJing Zheng

Key Points

  • The aim is to create a system that reverses the effects of Ticagrelor using engineered nanoparticles in vivo.
  • Developed boronic acid-functionalized gold nanoparticles.
  • Utilized o-carborane to enhance binding disruption of Ticagrelor.
  • Implemented a counterion-engineering strategy for improved solubility.
  • Tested efficacy in mouse and pig bleeding models.
  • Nanoparticles effectively neutralized Ticagrelor in vivo.
  • High efficacy demonstrated in both mouse and pig models.
  • Established a new framework for targeting cis-diols in biological systems.

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.

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Cite This Study

Yang et al. (2026) studied this question.

synapsesocial.com/papers/69b3aca302a1e69014cce7f6https://doi.org/10.1002/ange.202523384
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