A New Class of NIR‐II Gold Nanocluster‐Based Protein Biolabels for In Vivo Tumor‐Targeted Imaging

Abstract The design of bright NIR‐II luminescent nanomaterials that enable efficient labelling of proteins without disturbing their physiological properties in vivo is challenging. We developed an efficient strategy to synthesize bright NIR‐II gold nanoclusters (Au NCs) protected by biocompatible cyclodextrin (CD). Leveraging the ultrasmall size of Au NCs (<2 nm) and strong macrocycle‐based host–guest chemistry, the as‐synthesized CD‐Au NCs can readily label proteins/antibodies. Moreover, the labelled proteins/antibodies enable highly efficient in vivo tracking during blood circulation, without disturbing their biodistribution and tumor targeting ability, thus leading to a sensitive tumor‐targeted imaging. CD‐Au NCs are stable in the harsh biological environment and show good biocompatibility and high renal clearance efficiency. Therefore, the NIR‐II biolabels developed in this study provide a promising platform to monitor the physiological behavior of biomolecules in living organisms.