Studies On Functionalized Nano Metal Organic Framework(MOF) Materials For Uranium Decorporation In Vivo

In the past few years,the rapid development of the nuclear industry benefits humans,yet there are still some potential risks.Uranium is the main radioactive elements in the production of nuclear energy,and the exposure of uranium poses health risks to nuclear workers.In addition,the nuclear power plant accidents has brought public concerns regarding nuclear-related health hazards.For uranium internal contamination,the targeted organs such as kidneys and bone will be damaged due to its chemical toxicity and internal radiation.Using an effective chelator to reduce the accumulation of uranium in the body is considered as the most effective method up to date.At present,diethylenetriamine pentaacetate(DTPA)and sodium bicarbonate are recommended for the decontamination of uranium in vivo.However,DTPA ligands are effective against transuranic elements plutonium(Pu)and americium(Am),but ineffective for the uranium,while sodium bicarbonate is only effective in large doses that may lead to hypokalemia and alkalosis.Among the candidate ligands at the research stage,hydroxypyridinone(HOPO)ligands could effectively promote the excretion of uranium from the body,but some are still facing drawbacks such as fast metabolism and relatively high toxicity.Based on the disadvantages of molecular chelating agents,several nano decorporation agents was proposed in view of their advantages of long metabolic time in vivo and low biological toxicity.Different types of nano decorporation agents has been reported in our group for sequestering the internally contaminated uranium,such as surface-functionalized nano-chitosan(COS-HOPO,COS2LI-HOPO),nano MOF/COF chelating agents,nano-melanin-polymer,etc.Specially,metal-organic framework materials are selected for actinide decorporation due to their beneficial size and pore effect.Ui0-66-(COOH)4 prepared in our research group is a carboxyl functionalized nano-MOF(Ui0-66-(COOH)4),which exhibits high selectivity for uranyl as well as better decorporation efficiency than DTPA salt.However,the decorporation efficiency still needs to be improved.Therefore,this work intends to optimize the functionalization of nano metal-organic framework(MOF)materials to promote uranium removal ability.Based on the consideration of low toxicity and high adsorption potential of MOF materials,new nano-MOF materials were designed and synthesized in the aspects of metal centers,particle size,and functional groups.Specifically.a carboxyl group functionalized ZIF-71 material(ZIF-71-COOH)with endogenous Zn ion as the metal node and a HOPO functionalized MIL-101 material(MIL-101-HOPO)were obtained.The results are briefly introduced as follows:1)A nanoscale(～90 nm)zeolite imidazole ester skeleton material functionalized with endogenous zinc metal ion(Zn2+)as the metal node(ZIF-71-COOH,)was designed and synthesized via a ligand exchange reaction to optimize the decorporation efficiency and biosafety of the MOF material.FT-IR analysis confirms the successful exchange of the ligands.Furthermore,thermogravimetric analysis shows the high thermal stability of ZIF71-COOH which remains structurally stable up to 427℃.The results of the material stability experiments show that the material retains the structural integrity after 72 h immersion in HEPES buffer solution.The results of adsorption experiments show that 98%of uranyl was adsorbed and the adsorption equilibrium was achieved within 3 min.ZIF-71COOH was also able to specifically identify uranyl in selective adsorption experiments.Furthermore,the CCK-8 test proves that the cytotoxicity of ZIF-71-COOH was lower than that of clinically used ZnNa3-DTPA in the dosing range of 12.5-400 μg/mL.The results of the in vivo decorporation assays show that ZIF-71-COOH not only removed 50.7%of uranyl from the kidneys,but also achieved effective decorporation efficiency in femurs(26.5%)and liver(36.8%),respectively.For the ZnNa3-DTPA group,ZnNa3-DTPA did not show obvious decorporation efficacy on uranium in vivo,signifying the potential of nanoZIF in the field of actinides decorporation.2)To further optimize the decorporation efficacy,hydroxypyridinone ligands(HOPOs)with high affinity toward uranyl were modified into the nano-MOF.The aim of this work was to achieve rapid adsorption of uranium by taking the advantages of the excellent chelating effect of the HOPO functional group that are preorganized in the confined pores of nanosized MOF.The MOF with larger pore channel is required to accomodate HOPO ligands.Herein,a chromium-based nano-metal organic framework(nano-MOF)functionalized interiorly with 3,2-HOPO ligands,MIL-101-HOPO,was rationally synthesized via an amidation reaction.The transmission electron microscopy and dynamic light scattering analyses determine the morphology of polygonal flake with the particle size of～162 nm.In vitro adsorption experiments show that MIL-101-HOPO exhibited high adsorption selectivity and fast adsorption kinetics for uranyl,which could remove about 74%of the uranium from aqueous solutions within 10 min.Similarly,the CCK-8 test showed that the attachment of HOPO ligands simultaneously improved the metal binding ability and reduced the comprehensive toxicity of MIL-101-HOPO comparing to MIL-101-NH2.The results of in vivo uranyl decorporation assays reveal that MIL-101-HOPO with the decoration of HOPO ligands on the interior channel wall exhibited significantly increased uranyl removal ratio in kidneys comparing to the pristine nano-MOF,and was more effective than the clinically used ZnNa3-DTPA.All those results corroborate the interior functionalization of MOFs as an efficient strategy to develop promising uranyl decorporation agents.