MexBrain, Villeurbanne, France.
Institute of Light and Matter, UMR 5306, University of Lyon 1-CNRS, University of Lyon 1, Villeurbanne Cedex, France.
PLoS One. 2024 Apr 3;19(4):e0292414. doi: 10.1371/journal.pone.0292414. eCollection 2024.
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.
为了降低放射性同位素扩散的风险,开发预防和治疗措施尤其重要。对于大众治疗,开发的解决方案必须易于管理,最好是口服,具有针对广泛放射性同位素的有效、无毒的去放射性性质。目前,大多数口服螯合疗法产品很快被吸收到血液循环中,由于治疗的循环半衰期短,放射性同位素的螯合是一场与时间的赛跑。本报告提出了一种替代治疗方法,使用具有螯合性质的功能化壳聚糖(壳聚糖@DOTAGA),它在胃肠道内保持稳定,并通过粪便排出,从而可以防止摄入放射性同位素。该聚合物在不同 pH 值(从 1 到 7)下对不同重要的金属阳离子(包括(Cs(I)、Ir(III)、Th(IV)、Tl(I)、Sr(II)、U(VI)和 Co(II))表现出重要的体外螯合性质,代表了胃肠道内的不同环境。在口服壳聚糖@DOTAGA 后对铀污染的啮齿动物模型进行了体内概念验证。该聚合物部分防止了铀在肾脏内的积累(提供了保护作用),并完全防止了其在脾脏内的吸收。