Vacancies on 2D transition metal dichalcogenides elicit ferroptotic cell death

• Published in: Nature communications Vol. 11; no. 1; pp. 3484 - 14
• Main Authors: Xu, Shujuan, Zheng, Huizhen, Ma, Ronglin, Wu, Di, Pan, Yanxia, Yin, Chunyang, Gao, Meng, Wang, Weili, Li, Wei, Liu, Sijin, Chai, Zhifang, Li, Ruibin
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 13.07.2020; Nature Publishing Group UK; Nature Portfolio
• Subjects: Animals; Apoptosis; Biomarkers - metabolism; Blotting, Western; Cell death; Cell Death - genetics; Cell Death - physiology; Cell Line; Cell lines; Cell Survival - physiology; Chalcogenides; Endocytosis - physiology; Female; Ferroptosis; Ferroptosis - physiology; Glutathione; Glutathione peroxidase; Humans; Inflammation - metabolism; Interfaces; Lipid peroxidation; Lipids; Lungs; Macrophages; Mice, Inbred C57BL; Microscopy, Confocal; Molybdenum disulfide; Mortality; Movement disorders; Nanostructure; Nanotechnology; Neurodegenerative diseases; Parkinson's disease; Peroxidase; Peroxidation; Structure-Activity Relationship; Structure-activity relationships; Sulfide; THP-1 Cells; Transition metal compounds; Tumors; Vacancies
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-17300-7

Sustainable developments of nanotechnology necessitate the exploration of structure-activity relationships (SARs) at nano-bio interfaces. While ferroptosis may contribute in the developments of some severe diseases (e.g., Parkinson's disease, stroke and tumors), the cellular pathways and nano-SARs are rarely explored in diseases elicited by nano-sized ferroptosis inducers. Here we find that WS and MoS nanosheets induce an iron-dependent cell death, ferroptosis in epithelial (BEAS-2B) and macrophage (THP-1) cells, evidenced by the suppression of glutathione peroxidase 4 (GPX4), oxygen radical generation and lipid peroxidation. Notably, nano-SAR analysis of 20 transition metal dichalcogenides (TMDs) disclosures the decisive role of surface vacancy in ferroptosis. We therefore develop methanol and sulfide passivation as safe design approaches for TMD nanosheets. These findings are validated in animal lungs by oropharyngeal aspiration of TMD nanosheets. Overall, our study highlights the key cellular events as well as nano-SARs in TMD-induced ferroptosis, which may facilitate the safe design of nanoproducts.