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.

中文翻译：

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超小氧化铁纳米颗粒通过Beclin1 / ATG5依赖性自噬途径诱导肥大

铁基纳米颗粒可能引起肥大症，正在成为抑制肿瘤细胞生长的一种有前途的新方法。值得注意的是，已经发现超小氧化铁纳米粒子（USIONPs）会在胶质母细胞瘤（GBM）细胞中上调自噬过程。USIONPs是否也可以引发铁杆虫病，并且需要研究USIONPs诱导的自噬与铁杆虫病之间的关系。在当前的研究中，我们合成的具有良好水溶性的USIONPs可以显着上调GBM细胞中的肥大症标志物，并下调抗肥大症基因的表达。有趣的是，ferrostatin-1可以逆转USIONPs引起的肥大病，但凋亡，发烧或坏死的抑制剂却不能。同时，自噬抑制剂3-甲基腺嘌呤也可以逆转USIONPs引起的肥大病。此外，自噬过程上游基因Beclin1 / ATG5的shRNA沉默可以显着逆转USIONPs诱导的肥大病，而自噬过程的Beclin1 / ATG5的过表达则可以显着促进USIONPs诱导的肥大病。此外，溶酶体抑制剂可以显着逆转USIONPs引起的肥大症。总体而言，这些事实表明USIONPs诱导的肥大病是通过Beclin1 / ATG5依赖性自噬途径调控的。