In Vivo Uranium Decorporation by a Tailor-Made Hexadentate Ligand.

The sequestration of uranium, particularly from the deposited bones, has been an incomplete task in chelation therapy for actinide decorporation. Part of the reason is that all previous decorporation ligands are not delicately designed to meet the coordination requirement of uranyl cations. Herein, guided by DFT calculation, we elaborately design a hexadentate ligand (TAM-2LI-MAM2), whose preorganized planar oxo-donor configuration perfectly matches the typical coordination geometry of the uranyl cation. This leads to an ultrahigh binding affinity to uranyl supported by an in vitro desorption experiment of uranyl phosphate. Administration of this ligand by prompt intraperitoneal injection demonstrates its uranyl removal efficiencies from the kidneys and bones are up to 95.4% and 81.2%, respectively, which notably exceeds all the tested chelating agents as well as the clinical drug ZnNa3-DTPA, setting a new record in uranyl decorporation efficacy.

Self-Aggregated Nanoscale Metal-Organic Framework for Targeted Pulmonary Decorporation of Uranium.

The limited availability of effective agents for removing actinides from the lungs significantly restricts the effectiveness of medical treatments for nuclear emergencies. Inhalation is the primary route of internal contamination in 44.3% of actinide-related accidents, leading to the accumulation of radionuclides in the lungs and resulting in infections and potential tumor formation (tumorigenesis). This study focuses on the synthesis of a nanometal-organic framework (nMOF) material called ZIF-71-COOH, which is achieved by post-synthetic carboxyl functionalization of ZIF-71. The material demonstrates high and selective adsorption of uranyl, while also exhibiting increased particle size (≈2100 nm) when it aggregates in the blood, enabling passive targeting of the lungs through mechanical filtration. This unique property facilitates the rapid enrichment and selective recognition of uranyl, making nano ZIF-71-COOH highly effective in removing uranyl from the lungs. The findings of this study highlight the potential of self-aggregated nMOFs as a promising drug delivery system for targeted uranium decorporation in the lungs.