CNRS, ICN, Université côte d'Azur, 06108 Nice, France.
CEA, TIRO-MATOs, Université côte d'Azur, 06100 Nice, France.
Int J Mol Sci. 2022 Apr 25;23(9):4732. doi: 10.3390/ijms23094732.
In case of an incident in the nuclear industry or an act of war or terrorism, the dissemination of plutonium could contaminate the environment and, hence, humans. Human contamination mainly occurs via inhalation and/or wounding (and, less likely, ingestion). In such cases, plutonium, if soluble, reaches circulation, whereas the poorly soluble fraction (such as small colloids) is trapped in alveolar macrophages or remains at the site of wounding. Once in the blood, the plutonium is delivered to the liver and/or to the bone, particularly into its mineral part, mostly composed of hydroxyapatite. Countermeasures against plutonium exist and consist of intravenous injections or inhalation of diethylenetetraminepentaacetate salts. Their effectiveness is, however, mainly confined to the circulating soluble forms of plutonium. Furthermore, the short bioavailability of diethylenetetraminepentaacetate results in its rapid elimination. To overcome these limitations and to provide a complementary approach to this common therapy, we developed polymeric analogs to indirectly target the problematic retention sites. We present herein a first study regarding the decontamination abilities of polyethyleneimine methylcarboxylate (structural diethylenetetraminepentaacetate polymer analog) and polyethyleneimine methylphosphonate (phosphonate polymeric analog) directed against Th(IV), used here as a Pu(IV) surrogate, which was incorporated into hydroxyapatite used as a bone model. Our results suggest that polyethylenimine methylphosphonate could be a good candidate for powerful bone decontamination action.
在核工业事故或战争或恐怖主义行为的情况下,钚的传播可能会污染环境,从而危及人类。人类污染主要通过吸入和/或受伤(以及不太可能的摄入)发生。在这种情况下,如果钚可溶,则会到达循环系统,而难溶部分(如小胶体)则会被困在肺泡巨噬细胞中或留在受伤部位。一旦进入血液,钚就会被输送到肝脏和/或骨骼,特别是进入其矿物质部分,主要由羟磷灰石组成。针对钚的对策包括静脉注射或吸入二乙撑三胺五乙酸盐。然而,它们的有效性主要局限于可溶的循环形式的钚。此外,二乙撑三胺五乙酸的生物利用度短导致其迅速消除。为了克服这些限制并为这种常见疗法提供一种补充方法,我们开发了聚合物类似物来间接针对有问题的滞留部位。我们在此介绍了关于聚乙烯亚胺甲基羧酸酯(结构上的二乙撑三胺五乙酸聚合物类似物)和聚乙烯亚胺甲基膦酸酯(膦酸聚合物类似物)针对作为 Pu(IV) 替代物的 Th(IV) 的去污能力的第一项研究,Th(IV) 被掺入用作骨模型的羟磷灰石中。我们的结果表明,聚乙基亚胺甲基膦酸酯可能是一种强大的骨骼去污作用的良好候选物。