The toxicity mechanism of different sized iron nanoparticles on human breast cancer (MCF7) cells. Zhang Yuanxiao,Hai Yu,Miao Yuqing,Qi Xiao,Xue Weiming,Luo Yane,Fan Haiming,Yue Tianli Food chemistry 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. 10.1016/j.foodchem.2020.128263

Ultrasmall iron oxide nanoparticles induced ferroptosis via Beclin1/ATG5-dependent autophagy pathway. Wen Jian,Chen Hanren,Ren Zhongyu,Zhang Peng,Chen Jianjiao,Jiang Shulian Nano convergence Iron-based nanoparticles, which could elicit ferroptosis, is becoming a promising new way to inhibit tumor cell growth. Notably, ultrasmall iron oxide nanoparticles (USIONPs) have been found to upregulate the autophagy process in glioblastoma (GBM) cells. Whether USIONPs could also elicit ferroptosis and the relationship between the USIONPs-induced autophagy and ferroptosis need to be explored. In the current study, our synthesized USIONPs with good water solubility could significantly upregulate the ferroptosis markers in GBM cells, and downregulate the expression of anti-ferroptosis genes. Interestingly,ferrostatin-1 could reverse USIONPs- induced ferroptosis, but inhibitors of apoptosis, pyroptosis, or necrosis could not. Meanwhile, autophagy inhibitor 3-methyladenine could also reverse the USIONPs-induced ferroptosis. In addition, shRNA silencing of upstream genes Beclin1/ATG5 of autophagy process could significantly reverse USIONPs-induced ferroptosis, whereas overexpression of Beclin1/ATG5 of autophagy process could remarkably promote USIONPs-induced ferroptosis. Furthermore, lysosome inhibitors could significantly reverse the USIONPs-induced ferroptosis. Collectively, these facts suggest that USIONPs-induced ferroptosis is regulated via Beclin1/ATG5-dependent autophagy pathway. 10.1186/s40580-021-00260-z

Time-course effect of ultrasmall superparamagnetic iron oxide nanoparticles on intracellular iron metabolism and ferroptosis activation. Gao Jinling,Zhou Huige,Zhao Yanjie,Lu Lin,Zhang Jianzhong,Cheng Wenting,Song Xuxia,Zheng Yuxin,Chen Chunying,Tang Jinglong Nanotoxicology Ferroptosis is an iron-dependent cell death caused by excessive peroxidation of polyunsaturated fatty acids. It can be activated by iron-based nanoparticles as a potential cancer therapeutic target. However, the intracellular transformation of iron-based nanoparticles is still ambiguous and the subsequent ferroptosis mechanism is also obscure. Here, we identified the time-course metabolism of ultrasmall superparamagnetic iron oxide nanoparticles (USPIO) in cells by using X-ray absorption near edge structure spectroscopy. Also, the integrated quantitative transcriptome and proteome data obtained from the cells exposed to USPIO exhibited hallmark features of ferroptosis. With the chemical species of iron oxide transforming to ferritin, the intracellular GPX4 down-regulated, and lipid peroxide began to accumulate. These results provide evidence that the intracellular metabolism of USPIO induced ferroptosis in a time-dependent manner, and iron over-loaded in cytoplasm along with lipid peroxidation of the membrane are involved in the detailed mechanism of ferroptosis signaling activation. 10.1080/17435390.2021.1872112