Lomphithak Thanpisit, Helvacioglu Selin, Armenia Ilaria, Keshavan Sandeep, Ovejero Jesús G, Baldi Giovanni, Ravagli Costanza, Grazú Valeria, Fadeel Bengt
Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institutet, 17177 Stockholm, Sweden.
Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
Nanomaterials (Basel). 2023 May 24;13(11):1719. doi: 10.3390/nano13111719.
Ferroptosis, a form of iron-dependent, lipid peroxidation-driven cell death, has been extensively investigated in recent years, and several studies have suggested that the ferroptosis-inducing properties of iron-containing nanomaterials could be harnessed for cancer treatment. Here we evaluated the potential cytotoxicity of iron oxide nanoparticles, with and without cobalt functionalization (FeO and FeO@Co-PEG), using an established, ferroptosis-sensitive fibrosarcoma cell line (HT1080) and a normal fibroblast cell line (BJ). In addition, we evaluated poly (ethylene glycol) (PEG)-poly(lactic-co-glycolic acid) (PLGA)-coated iron oxide nanoparticles (FeO-PEG-PLGA). Our results showed that all the nanoparticles tested were essentially non-cytotoxic at concentrations up to 100 μg/mL. However, when the cells were exposed to higher concentrations (200-400 μg/mL), cell death with features of ferroptosis was observed, and this was more pronounced for the Co-functionalized nanoparticles. Furthermore, evidence was provided that the cell death triggered by the nanoparticles was autophagy-dependent. Taken together, the exposure to high concentrations of polymer-coated iron oxide nanoparticles triggers ferroptosis in susceptible human cancer cells.
铁死亡是一种铁依赖性、脂质过氧化驱动的细胞死亡形式，近年来已得到广泛研究，多项研究表明含铁纳米材料的铁死亡诱导特性可用于癌症治疗。在这里，我们使用已建立的、对铁死亡敏感的纤维肉瘤细胞系（HT1080）和正常成纤维细胞系（BJ），评估了有无钴功能化的氧化铁纳米颗粒（FeO和FeO@Co-PEG）的潜在细胞毒性。此外，我们还评估了聚（乙二醇）（PEG）-聚（乳酸-乙醇酸）（PLGA）包被的氧化铁纳米颗粒（FeO-PEG-PLGA）。我们的结果表明，所有测试的纳米颗粒在浓度高达100μg/mL时基本无细胞毒性。然而，当细胞暴露于更高浓度（200-400μg/mL）时，观察到具有铁死亡特征的细胞死亡，且这种情况在钴功能化的纳米颗粒中更为明显。此外，有证据表明纳米颗粒触发的细胞死亡是自噬依赖性的。综上所述，暴露于高浓度的聚合物包被氧化铁纳米颗粒会在易感人类癌细胞中引发铁死亡。
