Enhancing radioprotection: A chitosan-based chelating polymer is a versatile radioprotective agent for prophylactic and therapeutic interventions against radionuclide contamination

Arthur Durand (1, 2) , Tatiana Borisova (3) , François Lux (2, 4) , Jordyn Howard (1, 2) , Augustin Tillement (2, 5) , Halyna Kuznietsova (6) , Natalia Dziubenko (6) , Vladimir Lysenko (2) , Laurent David (7) , Daphné Morel (8) , Ross Berbeco (9, 10) , Serhiy Komisarenko (3) , Olivier Tillement (2) , Eric Deutsch (11)

1 MexBrain
2 iLM - FENNEC - iLM - Formation, élaboration de nanomatériaux et cristaux
3 Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine
4 IUF - Institut universitaire de France
5 Nano-H
6 Taras Shevchenko National University of Kyiv
7 IMP - Ingénierie des Matériaux Polymères
8 IGR - Institut Gustave Roussy
9 Brigham and Women’s Hospital [Boston, MA]
10 Dana-Farber Cancer Institute [Boston]
11 RaMo-IT - Radiothérapie Moléculaire et Innovation Thérapeutique

To mitigate the risk of radioactive isotope dissemination, the development of preventative and curative measures is of particular interest. For mass treatment, the developed solution must be easily administered, preferably orally, with effective, nontoxic decorporating properties against a wide range of radioactive isotopes. Currently, most orally administered chelation therapy products are quickly absorbed into the blood circulation, where chelation of the radioactive isotope is a race against time due to the short circulation half-life of the therapeutic. This report presents an alternative therapeutic approach by using a functionalized chitosan (chitosan@DOTAGA) with chelating properties that remains within the gastrointestinal tract and is eliminated in feces, that can protect against ingested radioactive isotopes. The polymer shows important in vitro chelation properties towards different metallic cations of importance, including (Cs(I), Ir(III), Th(IV), Tl(I), Sr(II), U(VI) and Co(II)), at different pH (from 1 to 7) representing the different environments in the gastrointestinal tract. An in vivo proof of concept is presented on a rodent model of uranium contamination following an oral administration of Chitosan@DOTAGA. The polymer partially prevents the accumulation of uranium within the kidneys (providing a protective effect) and completely prevents its uptake by the spleen.

Domaines: Polymères; Chimie de coordination; Chimie thérapeutique

Arthur Durand, Tatiana Borisova, François Lux, Jordyn Howard, Augustin Tillement, et al.. Enhancing radioprotection: A chitosan-based chelating polymer is a versatile radioprotective agent for prophylactic and therapeutic interventions against radionuclide contamination. PLoS ONE, 2024, 19 (4), pp.e0292414. ⟨10.1371/journal.pone.0292414⟩. ⟨hal-04567572⟩