To improve the bioimaging signal-to-noise ratio (SNR), long-term imaging capability, and decrease the potential biotoxicity, an in vivo cross-linking strategy was developed by using sub-10 nm, glutathione-modified, lanthanide nanoprobes. After administration, the nanoprobes cross-link in response to reactive oxygen species (ROS) at the inflamed area and enable the quick imaging of ROS in the second nearinfrared (NIR-II) window. These nanoprobes could be rapidly excreted due to their ultra-small size. This strategy may also be applied to other ultra-small contrast agents for the precise bioimaging by in situ lesion cross-linking. The authors of this work from Prof. Fan Zhang’s group in Department of Chemistry. To learn more about this work, please use the following link https://onlinelibrary.wiley.com/doi/10.1002/anie.201812878 (Angew. Chem. Int. Ed., 2019, 58(7), 2050-2054).