Bioactive NIR-II gold clusters for three-dimensional imaging and acute inflammation inhibition

Strong fluorescence and high catalytic activities cannot be achieved simultaneously due to conflicts in free electron utilization, resulting in a lack of bioactivity of most near-infrared-II (NIR-II) fluorophores. To circumvent this challenge, we developed atomically precise Au₂₂ clusters with strong NIR-II fluorescence ranging from 950 to 1300 nm exhibiting potent enzyme-mimetic activities through atomic engineering to create active Cu single-atom sites. The developed Au₂₁Cu₁ clusters show 18-fold higher antioxidant, 90-fold higher catalase-like, and 3-fold higher superoxide dismutase-like activities than Au₂₂ clusters, with negligible fluorescence loss. Doping with single Cu atoms decreases the bandgap from 1.33 to 1.28 eV by predominant contributions from Cu d states, and Cu with lost electron states effectuates high catalytic activities. The renal clearable clusters can monitor cisplatin-induced renal injury in the 20- to 120-minute window and visualize it in three dimensions using NIR-II light-sheet microscopy. Furthermore, the clusters inhibit oxidative stress and inflammation in the cisplatin-treated mouse model, particularly in the kidneys and brain.