Precision Metal Nanoclusters Meet Proteins: Crafting Next-Gen Hybrid Materials

Metal nanoclusters (NCs), owing to their atomic precision and unique molecule-like properties, have gained widespread attention for applications ranging from catalysis to bioimaging. In recent years, proteins, with their hierarchical structures and diverse functionalities, have emerged as good candidates for functionalizing metal NCs, rendering metal NC–protein conjugates with combined and even synergistically enhanced properties featured by both components. In this Perspective, we explore key questions regarding why proteins serve as complementary partners for metal NCs, the methodologies available for conjugating proteins with metal NCs, and the characterization techniques necessary to elucidate the structures and interactions within this emerging bionano system. We also highlight the emerging applications of metal NC–protein conjugates in biomedicine, catalysis, and biosensing in which the hybrid conjugates demonstrate remarkable performance. Furthermore, key challenges hampering further development of metal NC–protein conjugates, which include understanding binding mechanisms, expanding the diversity of proteins used for conjugation, and exploiting the individual roles of metal NCs and proteins within the hybrid systems, are discussed. This Perspective aims to systemize current synthetic methodologies and design principles for metal NC–protein conjugates, adding to their acceptance in precision nanotechnology.