Chelating Polymers for Targeted Decontamination of Actinides: Application of PEI-MP to Hydroxyapatite-Th(IV).

In case of an incident in the nuclear industry or an act of war or terrorism, the dissemination of plutonium could contaminate the environment and, hence, humans. Human contamination mainly occurs via inhalation and/or wounding (and, less likely, ingestion). In such cases, plutonium, if soluble, reaches circulation, whereas the poorly soluble fraction (such as small colloids) is trapped in alveolar macrophages or remains at the site of wounding. Once in the blood, the plutonium is delivered to the liver and/or to the bone, particularly into its mineral part, mostly composed of hydroxyapatite. Countermeasures against plutonium exist and consist of intravenous injections or inhalation of diethylenetetraminepentaacetate salts. Their effectiveness is, however, mainly confined to the circulating soluble forms of plutonium. Furthermore, the short bioavailability of diethylenetetraminepentaacetate results in its rapid elimination. To overcome these limitations and to provide a complementary approach to this common therapy, we developed polymeric analogs to indirectly target the problematic retention sites. We present herein a first study regarding the decontamination abilities of polyethyleneimine methylcarboxylate (structural diethylenetetraminepentaacetate polymer analog) and polyethyleneimine methylphosphonate (phosphonate polymeric analog) directed against Th(IV), used here as a Pu(IV) surrogate, which was incorporated into hydroxyapatite used as a bone model. Our results suggest that polyethylenimine methylphosphonate could be a good candidate for powerful bone decontamination action.

Carboxylate- and Phosphonate-Modified Polyethylenimine: Toward the Design of Actinide Decorporation Agents.

Plutonium (Pu) is an anthropogenic element involved in the nuclear industry cycle. Located at the bottom of the periodic table within the actinide family, it is a chemical toxic but also a radiological toxic, regardless of isotopy. After nearly 80 years of Pu industrialization, it has become clear that inhalation and wounds represent the two main ways a person may become contaminated after an accident. In order to reduce the deleterious health effects of Pu, it is crucial to limit chronic exposure by removing it or preventing its incorporation into the body. Diethylenetriaminepentaacetic acid (DTPA) has emerged as the gold standard for Pu decorporation, although it suffers from very short retention time in serum. Other molecules like the hydroxypyridonate family with high chemical affinity have also been considered. We have been considering alternative polymeric chelates and, in particular, polyethylenimine (PEI) analogues of DTPA (the carbonate or phosphonate version), which may present a real breakthrough in Pu decorporation not only because of their higher loading capacity but also because of their indirect vectorization properties correlated with a specific biodistribution into the lungs, bone, kidney, or liver. In the first part of this Forum Article, new data on the structural characterization of the complexation of PuIV with polyethylenimine methylphosphonate (PEI-MP) were obtained using the combination of extended X-ray absorption fine structure spectroscopy and ab initio molecular dynamics (AIMD) calculations. The use of thorium (Th) as a Pu chemical surrogate is also discussed because its unique oxidation state is IV+ in solution. In the second part of the paper, we put this new set of data on PEI-MP-Pu into perspective with use of the PEI platform to complex ThIV and PuIV. Uptake curves of ThIV witth polyethylenimine methylcarboxylate (PEI-MC) are compared with those of PEI-MP and DTPA, and the AIMD data are discussed.