Multiscale Bioresponses of Metal Nanoclusters.

Metal nanoclusters (NCs) are well-recognized novel nano-agents that hold great promise for applications in nanomedicine because of their ultrafine size, low toxicity, and high renal clearance. As foreign substances, however, an in-depth understanding of the bioresponses to metal NCs is necessary but is still far from being realized. Herein, this review is deployed to summarize the biofates of metal NCs at various biological levels, emphasizing their multiscale bioresponses at the molecular, cellular, and organismal levels. In the parts-to-whole schema, the interactions between biomolecules and metal NCs are discussed, presenting typical protein-dictated nano-bio interfaces, hierarchical structures, and in vivo trajectories. Then, the accumulation, internalization, and metabolic evolution of metal NCs in the cellular environment and as-imparted theranostic functionalization are demonstrated. The organismal metabolism and transportation processes of the metal NCs are subsequently distilled. Finally, this review ends with the conclusions and perspectives on the outstanding issues of metal NC-mediated bioresponses in the near future. This review is expected to provide inspiration for tailoring the customization of metal NC-based nano-agents to meet practical requirements in different sectors of nanomedicine.