Sub-2.5-nm amidoxime metal-organic frameworks alleviate uranium-induced nephrotoxicity

Functionalized micro-/nanoscale metal-organic frameworks (MOFs) hold significant potential in treating uranium-contaminated water and extracting uranium from seawater, but their application in vivo as decorporation agents for uranium-induced nephrotoxicity is fundamentally restricted by the size-dependent glomerular filtration barrier. Herein, we report a one-pot controllable synthesis of amidoxime MOFs with diameters of sub-2.5 nm. The subnanometer dimension enabled precise renal targeting of the MOFs and delivery to proximal tubules, the primary site of uranium deposition. In uranium internal contamination mouse models, delayed treatment with amidoxime MOFs resulted in an 82.5% reduction in renal uranium accumulation, outperforming all currently reported chelating agents, as well as the clinical drug ZnNa 3 -DTPA, and thus significantly alleviated uranium-induced nephrotoxicity. This subnanometer-scale engineering approach represents a groundbreaking paradigm for the defense against radionuclide-induced nephrotoxicity.