Bibb Emory, Alajlan Noura, Alsuwailem Saad, Mitchell Benjamin, Brady Amy, Maqbool Muhammad, George Remo
Nuclear Medicine and Molecular Imaging Sciences Program, Department of Clinical and Diagnostic Sciences, School of Health Professions, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Health Physics Program, Department of Clinical and Diagnostic Sciences, School of Health Professions, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Biology (Basel). 2021 Nov 8;10(11):1148. doi: 10.3390/biology10111148.
Owing to its unique redox properties, cerium oxide (nanoceria) nanoparticles have been shown to confer either radiosensitization or radioprotection to human cells. We investigated nanoceria's ability to modify cellular health and reactive oxygen species (ROS) at various absorbed doses (Gray) of ionizing radiation in MDA-MB231 breast carcinoma cells. We used transmission electron microscopy to visualize the uptake and compartmental localization of nanoceria within cells at various treatment concentrations. The effects on apoptosis and other cellular health parameters were assessed using confocal fluorescence imaging and flow cytometry without and with various absorbed doses of ionizing radiation, along with intracellular ROS levels. Our results showed that nanoceria were taken up into cells mainly by macropinocytosis and segregated into concentration-dependent large aggregates in macropinosomes. Confocal imaging and flow cytometry data showed an overall decrease in apoptotic cell populations in proportion to increasing nanoparticle concentrations. This increase in cellular health was observed with a corresponding reduction in ROS at all tested absorbed doses. Moreover, this effect appeared pronounced at lower doses compared to unirradiated or untreated populations. In conclusion, internalized nanoceria confers radioprotection with a corresponding decrease in ROS in MDA-MB231 cells, and this property confers significant perils and opportunities when utilized in the context of radiotherapy.
由于其独特的氧化还原特性，氧化铈（纳米氧化铈）纳米颗粒已被证明可对人类细胞产生放射增敏或辐射防护作用。我们研究了纳米氧化铈在不同吸收剂量（戈瑞）的电离辐射下对MDA-MB231乳腺癌细胞的细胞健康和活性氧（ROS）的影响。我们使用透射电子显微镜观察了不同处理浓度下纳米氧化铈在细胞内的摄取和区室定位。在有无不同吸收剂量的电离辐射情况下，使用共聚焦荧光成像和流式细胞术评估了对细胞凋亡和其他细胞健康参数的影响，同时还检测了细胞内ROS水平。我们的结果表明，纳米氧化铈主要通过巨胞饮作用被细胞摄取，并在巨胞饮小体中分离成浓度依赖性的大聚集体。共聚焦成像和流式细胞术数据显示，凋亡细胞群体总体上随着纳米颗粒浓度的增加而减少。在所有测试的吸收剂量下，随着细胞健康状况的改善，ROS相应减少。此外，与未辐照或未处理的群体相比，这种效应在较低剂量下更为明显。总之，内化的纳米氧化铈在MDA-MB231细胞中具有辐射防护作用，同时ROS相应减少，并且在放射治疗中利用这一特性会带来重大风险和机遇。
