Christophe Den Auwer - Université Côte D’Azur, CNRS, Institut de Chimie de Nice - Keywords: Actinide contamination

Christophe Den Auwer - Université Côte D’Azur, CNRS, Institut de Chimie de Nice - Keywords: Actinide contamination

Contribution title: New paradigms in nuclear human decorporation using macromolecular systems

The use of uranium and to a minor extent plutonium as a fuel for nuclear energy production or as components in military applications is under increasing public pressure. Associated nuclear risks include chronic or acute contamination in the nuclear industry, exposure in case of major accident or military attack, chronic low (to very low) dose effects from naturally (uranium) or artificially contaminated backgrounds. Public perception of those risks is by far a questioning by itself because it is dependent of various sociological factors like political culture, education, and political stability.... Uranium (U) is weakly radioactive in its natural isotopy but its chemical toxicity, combined with its large scale industrial utilization, makes it a source of concern in terms of health impact for workers and possibly for the general population. Plutonium (Pu) is an artificial element that exhibits both chemical and radiological toxicities for all isotopes. In all cases, after human exposure, plutonium and uranium will be retained in main target organs (liver, kidneys) as well as skeleton although they exhibit differences in their biodistribution. In case of human contamination, treatments currently available are either inefficient or not very selective. Today, the only decorporation drug used in France is DTPA (diethylenetriaminepentaacetic acid, calcium form) injected intravenously. Although its complexing constant is strong for Pu(IV) it is rather poor for U(VI) and it has little chemical specificity. As a consequence it is only valid for removing actinide contamination from blood, few minutes after contamination. In order to overcome these difficulties, news strategies or paradigms must be elaborated.
Macromolecular systems like biocompatible polymers or reticulated nanoparticules could represent an alternative strategy because of their tropism for specific target organs (bone, lungs, liver, kidneys...). For the skeleton for instance, we have recently addressed the complexation properties of methylcarboxylated and methylphosphonated polyethyleneimine with uranium and plutonium. For the pulmonary alveolar system, we have explored the design of biocompatible chitosan nanoparticles able to release the decorporation agent directly into the macrophages and specifically target the poor soluble forms of plutonium. For both systems, physical chemical data has been obtained using a combination of analytical and spectroscopic techniques in order to fully characterize the complexation site. In the case of uranium, molecular dynamics simulation has been used as a complement to better understand the polymer arrangement around the uranium cation. This structural data has been further compared to the well-known DTPA system.
Studies aiming at determining the optimal molecular weight which directly impacts biodistribution and long-term kinetics experiments are also required to determine whether or not the actinide complexes could be naturally excreted with time. But in any case the physical chemical approach described here represents a necessary basic chemistry stage before envisioning further biological evaluations.