Vacancies on 2D transition metal dichalcogenides elicit ferroptotic cell death

Nature Communications - Tập 11 Số 1
Shujuan Xu1, Huizhen Zheng1, Ronglin Ma1, Di Wu1, Yanxia Pan1, Chunyang Yin2, Meng Gao1, Weili Wang1, Wei Li1, Sijin Liu2, Zhifang Chai1, Ruibin Li1
1State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, Jiangsu, China
2State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, 18 Shuangqing Road, Beijing, 100085, China

Tóm tắt

AbstractSustainable 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 WS2 and MoS2 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.

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Tài liệu tham khảo

Lee, J.-H. et al. General and programmable synthesis of hybrid liposome/metal nanoparticles. Sci. Adv. 2, e1601838 (2016).

Xue, X. et al. Trojan Horse nanotheranostics with dual transformability and multifunctionality for highly effective cancer treatment. Nat. Commun. 9, 3653 (2018).

Nagai, H. et al. Diameter and rigidity of multiwalled carbon nanotubes are critical factors in mesothelial injury and carcinogenesis. Proc. Natl Acad. Sci. USA. 108, E1330–1338 (2011).

Li, R. et al. Interference in autophagosome fusion by rare earth nanoparticles disrupts autophagic flux and regulation of an interleukin-1β producing inflammasome. ACS Nano 8, 10280–10292 (2014).

Cai, X. et al. Multi-hierarchical profiling the structure-activity relationships of engineered nanomaterials at nano-bio interfaces. Nat. Commun. 9, 4416 (2018).

Li, R. et al. Surface oxidation of graphene oxide determines membrane damage, lipid peroxidation, and cytotoxicity in macrophages in a pulmonary toxicity model. ACS Nano 12, 1390–1402 (2018).

Gao, M. et al. Two-dimensional Tin Selenide (SnSe) nanosheets capable of mimicking key dehydrogenases in cellular metabolism. Angew. Chem. 9, 3647–3652 (2020).

Chng, E. L., Sofer, Z. & Pumera, M. MoS2 exhibits stronger toxicity with increased exfoliation. Nanoscale 6, 14412–14418 (2014).

Wang, X. et al. Differences in the toxicological potential of 2D versus aggregated molybdenum disulfide in the lung. Small 11, 5079–5087 (2015).

McManus, D. et al. Water-based and biocompatible 2D crystal inks for all-inkjet-printed heterostructures. Nat. Nanotechnol. 12, 343–350 (2017).

Mei, L. et al. Translocation, biotransformation-related degradation, and toxicity assessment of polyvinylpyrrolidone modified 2H nano-MoS2. Nanoscale 11, 4767–4780 (2019).

Stockwell, B. R. et al. Ferroptosis: a regulated cell death nexus linking metabolism, redox biology, and disease. Cell 171, 273–285 (2017).

Guiney, S. J., Adlard, P. A., Bush, A. I., Finkelstein, D. I. & Ayton, S. Ferroptosis and cell death mechanisms in Parkinson’s disease. Neurochem. Int. 104, 34–48 (2017).

Alim, I. et al. Selenium drives a transcriptional adaptive program to block ferroptosis and treat stroke. Cell 177, 1262–1279 (2019).

Voorde, J. V. et al. Improving the metabolic fidelity of cancer models with a physiological cell culture medium. Sci. Adv. 5, eaau7314 (2019).

Mai, T. T. et al. Salinomycin kills cancer stem cells by sequestering iron in lysosomes. Nat. Chem. 9, 1025–1033 (2017).

Kim, S. E. et al. Ultrasmall nanoparticles induce ferroptosis in nutrient-deprived cancer cells and suppress tumour growth. Nat. Nanotechnol. 11, 977–985 (2016).

Chowdhury, R. K., Maiti, R., Ghorai, A., Midya, A. & Ray, S. K. Novel silicon compatible p-WS2 2D/3D heterojunction devices exhibiting broadband photoresponse and superior detectivity. Nanoscale 8, 13429–13436 (2016).

Zhang, H. et al. Molybdenum disulfide (MoS2) as a broadband saturable absorber for ultra-fast photonics. Opt. Express 22, 7249–7260 (2014).

Chen, C.-H. et al. Hole mobility enhancement and p-doping in monolayer WSe2 by gold decoration. 2D Mater. 1, 034001 (2014).

Rosenberger, M. R., Chuang, H.-J., McCreary, K. M., Hanbicki, A. T., Sivaram, S. V. & Jonker, B. T. Nano-“squeegee” for the creation of clean 2D material interfaces. ACS Appl. Mater. Interfaces 10, 10379–10387 (2018).

Geng, R. et al. Bio-inspired synthesis of highly crystallized hexagonal boron nitride nanosheets. Ceram. Int. 44, 14228–14235 (2018).

Hong, J. et al. Nitric oxide production by the vacuolar-type (H+)-ATPase inhibitors bafilomycin A and concanamycin A and its possible role in apoptosis in RAW 264.7 cells. J. Pharmacol. Exp. Ther. 319, 672–681 (2006).

Chung, H. et al. NLRP3 regulates a non-canonical platform for caspase-8 activation during epithelial cell apoptosis. Cell Death Differ. 23, 1331–1346 (2016).

Zhang, G., Wang, G., Liu, Y., Liu, H., Qu, J. & Li, J. Highly active and stable catalysts of phytic acid-derivative transition metal phosphides for full water splitting. J. Am. Chem. Soc. 138, 14686–14693 (2016).

Hirayama, T., Okuda, K. & Nagasawa, H. A highly selective turn-on fluorescent probe for iron (II) to visualize labile iron in living cells. Chem. Sci. 4, 1250–1256 (2013).

Feng, H. et al. Transferrin receptor is a specific ferroptosis marker. Cell Rep. 30, 3411–3423.e7 (2020).

Gao, M., Monian, P., Quadri, N., Ramasamy, R. & Jiang, X. Glutaminolysis and transferrin regulate ferroptosis. Mol. Cell 59, 298–308 (2015).

Ma, S., Henson, E., Chen, Y. & Gibson, S. Ferroptosis is induced following siramesine and lapatinib treatment of breast cancer cells. Cell Death Dis. 7, e2307 (2016).

Puzyn, T., Leszczynska, D. & Leszczynski, J. Toward the development of “nano-QSARs”: advances and challenges. Small 22, 2494–5099 (2009).

Liu, R. et al. Classification NanoSAR development for cytotoxicity of metal oxide nanoparticles. Small 8, 1118–1126 (2011).

Chee, S.-S. Sulfur vacancy-induced reversible doping of transition metal disulfides via hydrazine treatment. Nanoscale 9, 9333–9339 (2017).

Sim, D. M. et al. Controlled doping of vacancy-containing few-layer MoS2 via highly stable thiol-based molecular chemisorption. ACS Nano 12, 12115–12123 (2015).

Amani, M. et al. Near-unity photoluminescence quantum yield in MoS2. Science 350, 1065–1068 (2015).

Velusamy, D. B. et al. Flexible transition metal dichalcogenide nanosheets for band-selective photodetection. Nat. Commun. 6, 8063 (2015).

Kang, K. et al. High-mobility three-atom-thick semiconducting films with wafer-scale homogeneity. Nature 520, 656–660 (2015).

Ciarrocchi, A., Avsar, A., Ovchinnikov, D. & Kis, A. Thickness-modulated metal-to-semiconductor transformation in a transition metal dichalcogenide. Nat. Commun. 9, 919 (2018).

Berghauser, G. et al. Inverted valley polarization in optically excited transition metal dichalcogenides. Nat. Commun. 9, 971 (2018).

Cao, T. et al. Valley-selective circular dichroism of monolayer molybdenum disulphide. Nat. Commun. 3, 887 (2012).

Yu, W. J. et al. Unusually efficient photocurrent extraction in monolayer van der Waals heterostructure by tunnelling through discretized barriers. Nat. Commun. 7, 13278 (2016).

Agnihotri, P., Dhakras, P. & Lee, J. U. Bipolar junction transistors in two-dimensional WSe2 with large current and photocurrent gains. Nano Lett. 16, 4355–4360 (2016).

Kang, T. W. et al. 2D transition metal dichalcogenides with glucan multivalency for antibody-free pathogen recognition. Nat. Commun. 9, 2549 (2018).

Cai, X. et al. Molecular mechanisms, characterization methods and utilities of nanoparticle biotransformation in nanosafety assessments. Small, 1907663 (2020).

Caracciolo, G. et al. Stealth effect of biomolecular corona on nanoparticle uptake by immune cells. Langmuir 31, 10764–10773 (2015).

Huang, Y. et al. Quantitative structure-activity relationship models for predicting inflammatory potential of metal oxide nanoparticles. Environ. Health Perspect, https://doi.org/10.1289/EHP6508 (2020).

Wang, X. et al. Quantitative techniques for assessing and controlling the dispersion and biological effects of multiwalled carbon nanotubes in mammalian tissue culture cells. ACS Nano 4, 7241–7252 (2010).

Vadivelmurugan, A., Anbazhagan, R., Arunagiri, V., Laiab, J.-Y. & Tsai, H.-C. Pluronic F127 self-assembled MoS2 nanocomposites as an effective glutathione responsive anticancer drug delivery system. RSC Adv. 9, 25592 (2019).

Wu, S., Liu, X., Ren, J. & Qu, X. Glutathione depletion in a Benign manner by MoS2-based nanoflowers for enhanced hypoxia-irrelevant free-radical-based cancer therapy. Small 15, e1904870 (2019).

Loke J. Pathophysiology and Treatment of Inhalation Injuries. (Yale University School of Medicine. Press, New Haven, 1986).

Cai, X. et al. Reduction of pulmonary toxicity of metal oxide nanoparticles by phosphonate-based surface passivation. Part. Fibre Toxicol. 14, 13 (2017).

Li, R. et al. Surface charge and cellular processing of covalently functionalized multiwall carbon nanotubes determine pulmonary toxicity. ACS Nano 7, 2352–7368 (2013).

Tsang, M. P., Kikuchi-Uehara, E., Sonnemann, G. W., Aymonier, C. & Hirao, M. Evaluating nanotechnology opportunities and risks through integration of life-cycle and risk assessment. Nat. Nanotechnol. 12, 734–739 (2017).