Weak Anchoring Sites of Thiolate‐Protected Luminescent Gold Nanoparticles

Abstract Surface functionalization of gold nanoparticles (AuNPs) with thiolate ligands is a successful strategy for controlling their stability, nanotoxicity, circulation, and interaction with biological environments as leading nanomedicines. However, the effects of the weak anchoring groups of NH₂ and COOH have been long‐term ignored because of the well‐recognized strong anchoring site of S–Au. Herein, the authors achieve controllable weak anchoring sites of the luminescent AuNPs using a typical thiolate peptide such as glutathione with anchoring groups of SH, COOH, and NH₂. Additionally, they establish that not only the strong anchoring site of S–Au, but also the weak anchoring sites from N‐Au and COO–Au are critical to the behavior of AuNPs at both in vitro and in vivo levels. These results open up new possibilities for the fundamental understanding of the significance of the weak anchoring sites in the future surface functionalization of nanomedicines toward advanced theranostics.