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

PLoS One. 2024 Apr 3;19(4):e0292414. doi: 10.1371/journal.pone.0292414. eCollection 2024.

Abstract

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.

MeSH terms

  • Chelating Agents / chemistry
  • Chitosan* / chemistry
  • Polymers
  • Radiation-Protective Agents* / pharmacology
  • Uranium* / chemistry

Substances

  • Chitosan
  • Uranium
  • Radiation-Protective Agents
  • Polymers
  • Chelating Agents

Grants and funding

This work was partially supported by EU Horizon 2020 Research and Innovation Staff Exchange Program (RISE) under Marie Skłodowska-Curie Action (project “UNAT” №101008159). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. MexBrain and Nano-H companies funded this research in the form of authors salaries (A. D. and J. H., PhD students, for MexBrain and A. T., PhD student, for Nano-H) and material research, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.