Proskurnina Elena V, Sozarukova Madina M, Ershova Elizaveta S, Savinova Ekaterina A, Kameneva Larisa V, Veiko Natalia N, Saprykin Vladimir P, Vyshegurov Khamzat K, Ivanov Vladimir K, Kostyuk Svetlana V
Kurnakov Institute of General and Inorganic Chemistry of the Russian Academy of Sciences, Moscow 119071, Russia.
Faculty of Chemistry, Biology and Biotechnology, North Ossetian State University Named After Kosta Levanovich Khetagurov, Vladikavkaz 362025, Russia.
Molecules. 2025 Jul 23;30(15):3078. doi: 10.3390/molecules30153078.
Nanoceria is a multifaceted enzyme-like catalyst of ROS-mediated (reactive oxygen species) reactions, which results in its multiple biomedical applications. Biodegradable polysaccharide coatings improve biocompatibility, while the effects of these coatings on the ROS-related activity of nanoceria in cells need thorough studies. Here, we used human embryonic lung fibroblasts to study the effects of maltodextrin and chitosan coatings on cellular oxidative metabolism of nanoceria by examining cell viability, mitochondrial potential, accumulation of nanoparticles in cells, intracellular ROS, expression of NOX4 (NADPH oxidase 4), NRF2 (nuclear factor erythroid 2-related factor 2), NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells), and STAT3 (signal transducer and activator of transcription 3) proteins as well as the expression of biomarkers of DNA damage/repair, cell proliferation, and autophagy. Both types of polysaccharide-coated nanoceria were non-toxic up to millimolar concentrations. For maltodextrin-coated nano-CeO, in contrast to bare nanoparticles, there was no oxidative DNA damage/repair with moderate activation of NOX4 expression. Like bare nanoceria, maltodextrin-coated nanoparticles demonstrate the proliferative impact and do not activate autophagy. However, maltodextrin-coated nanoparticles have an activating impact on mitochondrial potential and the NF-κB pathway. Chitosan-coated nanoceria causes short-term intracellular oxidative stress, activation of the expression of NOX4, STAT3, and NRF2, oxidative DNA damage, and double-strand breaks accompanied by activation of DNA repair systems. In contrast to maltodextrin-coated nanoparticles, chitosan-coated nanoceria inhibits the NF-κB pathway and activates autophagy. These findings would be useful in the development of advanced nanoceria-based pharmaceuticals and contribute to the understanding of the biochemical properties of nanoceria as a modulator of ROS-dependent signaling pathways.
纳米氧化铈是一种多方面类似酶的活性氧（ROS）介导反应的催化剂，这使其具有多种生物医学应用。可生物降解的多糖涂层可提高生物相容性，然而这些涂层对细胞中纳米氧化铈的ROS相关活性的影响需要深入研究。在此，我们使用人胚肺成纤维细胞，通过检测细胞活力、线粒体电位、纳米颗粒在细胞内的积累、细胞内ROS、NOX4（烟酰胺腺嘌呤二核苷酸磷酸氧化酶4）、NRF2（核因子红细胞2相关因子2）、NF-κB（活化B细胞的核因子κ轻链增强子）和STAT3（信号转导和转录激活因子3）蛋白的表达以及DNA损伤/修复、细胞增殖和自噬的生物标志物的表达，来研究麦芽糖糊精和壳聚糖涂层对纳米氧化铈细胞氧化代谢的影响。两种类型的多糖包被纳米氧化铈在毫摩尔浓度以下均无毒。对于麦芽糖糊精包被的纳米CeO，与裸露的纳米颗粒相比，在NOX4表达适度激活的情况下没有氧化DNA损伤/修复。与裸露的纳米氧化铈一样，麦芽糖糊精包被的纳米颗粒具有增殖作用且不激活自噬。然而，麦芽糖糊精包被的纳米颗粒对线粒体电位和NF-κB途径有激活作用。壳聚糖包被的纳米氧化铈会引起短期细胞内氧化应激、NOX4、STAT3和NRF2表达的激活、氧化DNA损伤和双链断裂，并伴有DNA修复系统的激活。与麦芽糖糊精包被的纳米颗粒相比，壳聚糖包被的纳米氧化铈抑制NF-κB途径并激活自噬。这些发现将有助于先进的纳米氧化铈基药物的开发，并有助于理解纳米氧化铈作为ROS依赖性信号通路调节剂的生化特性。
