Yuanxiao Zhang;Yu Hai;Yuqing Miao;Xiao Qi;Weiming Xue;Yane Luo;Haiming Fan;Tianli Yue
The toxicity mechanism of superparamagnetic iron oxide nanoparticles (SPIONs) were examined multidimensionally to reduce the toxicity risks. A higher dosage and more suitable size of SPIONs enhanced the uptake amount into MCF7 cells, leading to a higher specific uptake rate of SPIONs with the formation of more reactive oxygen species (ROS). ROS was an intrinsic factor of cell death. Interestingly, the smaller SPIONs (S1) liked to produce more ROS in mitochondria to damage mitochondria, while the larger SPIONs (S2 and S3) promoted ROS yield in plasma to destroy cytomembrane. Furthermore, ROS synthesis pathways were the partial of cell death pathways, and ferroptosis pathway was the main contributor to mitochondrial and cytomembrane damage. Meanwhile, ROS amount was well coincided to gene expression level of these cell death pathways, which inferred RNA-seq might be a new method to evaluate the oxidative stress and potential toxicity of nanomaterials.