Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region 142290, Russia.
University of Georgia, 315 Dawson Hall, Athens, GA 30602, USA.
Molecules. 2020 Jun 27;25(13):2957. doi: 10.3390/molecules25132957.
Cerium oxide nanoparticles (nanoceria) are believed to be the most versatile nanozyme, showing great promise for biomedical applications. At the same time, the controlled intracellular delivery of nanoceria remains an unresolved problem. Here, we have demonstrated the radioprotective effect of polyelectrolyte microcapsules modified with cerium oxide nanoparticles, which provide controlled loading and intracellular release. The optimal (both safe and uptake efficient) concentrations of ceria-containing microcapsules for human mesenchymal stem cells range from 1:10 to 1:20 cell-to-capsules ratio. We have revealed the molecular mechanisms of nanoceria radioprotective action on mesenchymal stem cells by assessing the level of intracellular reactive oxygen species (ROS), as well as by a detailed 96-genes expression analysis, featuring genes responsible for oxidative stress, mitochondrial metabolism, apoptosis, inflammation etc. Hybrid ceria-containing microcapsules have been shown to provide an indirect genoprotective effect, reducing the number of cytogenetic damages in irradiated cells. These findings give new insight into cerium oxide nanoparticles' protective action for living beings against ionising radiation.
氧化铈纳米颗粒（纳米铈）被认为是最通用的纳米酶，在生物医学应用中具有广阔的前景。与此同时，纳米铈的细胞内可控递送仍然是一个未解决的问题。在这里，我们展示了用氧化铈纳米颗粒修饰的聚电解质微胶囊的放射防护作用，它提供了可控的装载和细胞内释放。对于人骨髓间充质干细胞，含氧化铈微胶囊的最佳（安全且摄取效率高）浓度范围为 1:10 到 1:20 个细胞到胶囊的比例。我们通过评估细胞内活性氧（ROS）的水平以及详细的 96 个基因表达分析，揭示了纳米铈对间充质干细胞的放射防护作用的分子机制，这些分析涉及负责氧化应激、线粒体代谢、细胞凋亡、炎症等的基因。杂交含氧化铈微胶囊已被证明具有间接的基因保护作用，减少了辐照细胞中的细胞遗传学损伤数量。这些发现为氧化铈纳米颗粒对生物体的放射防护作用提供了新的见解。
