PlutoPoly

Nuclear contamination of humans can occur in different contexts, such as nuclear plant accidents (such as the Chernobyl event), military conflicts, terrorism, etc. The problematic radioactive elements that may be released include the “actinides”, among which plutonium is one of the most harmful to human health. In case of accidental plutonium contamination, almost half of the contamination occurs through inhalation, and the lungs eventually retain more than 90% of the inhaled radioactivity. Currently, there is no efficient treatment to prevent and cure such contamination of the lungs. This project aims at developing a new class of compounds for treatment purposes, to help patients recover from plutonium lung contamination.

Lungs preferentially retain radioactive contamination because they have specific cells, the alveolar macrophages, which capture and retain toxic elements that enter the lungs. We have thus developed new molecules that are able to bind (i.e., chelate) the plutonium atoms trapped in the alveolar macrophages. These chelating molecules are polymers made from amino-carboxylates. We have developed several forms of polymers, each consisting of a branched polyethylenimine bearing three chelate groups per monomer.

We performed a series of dose-response tests in vitro (tests for toxicological assessment), putting together different amounts of polymers with lung macrophages. Transmission Electronic Microscopy images of the tested macrophages revealed massive phagocytosis (capture) of the polymers by the macrophages. Other tests showed that the chelating polymers successfully bound actinides in vitro, and plutonium in particular. We are now in the process of developing a more complete biological test to analyze the ability of the new chelating polymers to capture actinides inside macrophages. Overall, these tests will be crucial to determine the abilities of the new chelating polymers to (i) penetrate the lung macrophages, (ii) form complexes with actinides, and (iii) escape the lung system to be eliminated by urinary excretion.