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<p>Precise surface engineering of gold nanoclusters (Au NCs) is critical for bioimaging. However, conventional methods often compromise the structural integrity of Au NCs or result in uncontrolled ligand distribution due to rapid reaction kinetics and etching side reactions. Herein, we develop an interphase-assisted ligand exchange method, which leverages mass transfer resistance between immiscible phases to precisely control the mass transfer of ligands. This approach significantly suppresses side etching while maintaining exchange kinetics, enabling high-yield, structure-preserving substitution of diverse thiol ligands on Au NCs. By systematically introducing <i>p</i>-aminothiophenol (<i>p</i>-ATP) ligands, we reveal that increasing <i>p</i>-ATP density on Au<sub>25</sub> NCs shifts their biodistribution in female BALB/c nude mice from liver and spleen to kidneys, highlighting the tunability of organ targeting through ligand engineering. The methodology developed here not only boosts the surface engineering to molecular resolution, but also provides a platform for studying ligand effects of metal nanomaterials at the same resolution.</p>

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Atomically precise ligand engineering of gold nanoparticles via interphase mass transfer

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年1月12日

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  • Bihan Zhang,
  • Feng Xiao,
  • Xiaorong Song,
  • Moshuqi Zhu,
  • Qiaofeng Yao,
  • Jianping Xie

摘要

Precise surface engineering of gold nanoclusters (Au NCs) is critical for bioimaging. However, conventional methods often compromise the structural integrity of Au NCs or result in uncontrolled ligand distribution due to rapid reaction kinetics and etching side reactions. Herein, we develop an interphase-assisted ligand exchange method, which leverages mass transfer resistance between immiscible phases to precisely control the mass transfer of ligands. This approach significantly suppresses side etching while maintaining exchange kinetics, enabling high-yield, structure-preserving substitution of diverse thiol ligands on Au NCs. By systematically introducing p-aminothiophenol (p-ATP) ligands, we reveal that increasing p-ATP density on Au25 NCs shifts their biodistribution in female BALB/c nude mice from liver and spleen to kidneys, highlighting the tunability of organ targeting through ligand engineering. The methodology developed here not only boosts the surface engineering to molecular resolution, but also provides a platform for studying ligand effects of metal nanomaterials at the same resolution.