Engineering Ion‐Specific Coordination Environments via Multi‐Ion Imprinting for In Vivo Decorporation of Multiple Radionuclides

ABSTRACT The risk of radionuclide exposure is increasing due to the rapid development of nuclear energy worldwide. However, no effective therapies exist for internal contamination with multiple radionuclides, hindering the safe development of nuclear energy. Here, we report a multi‐ion imprinting strategy to construct a nanocage chelator with tailored recognition sites. The incorporation of templates (UO 2 2+ , Th 4+ , Sr 2+ , and Pb 2+ ) into the metal‐organic framework directs the formation of heterogeneous coordination environments with strong affinity and spatial configurations matched to target cations. The resulting template‐removed MOFs (RMMOF) show fast uptake kinetics, removing over 90% of each radionuclide within 20 min, even in the presence of 12‐fold excess interfering ions. Synchrotron radiation spectrum analysis and calculation suggest that the radionuclides are immobilized as single‐atomically dispersed coordination species within the framework and the free carboxyl and amino groups cooperatively form distinct coordination configurations with different radionuclides. Importantly, in vivo studies demonstrate efficient simultaneous decorporation of four radionuclides, with removal efficiencies of 40%–75% in major deposition organs, far exceeding the clinically used DTPA. This work establishes multi‐ion imprinting in MOFs as a viable strategy for the tailored synthesis of broad‐spectrum decorporation agents, offering a promising approach for the treatment of internal radionuclide contamination.