The DOI matches its Crossref record; 71 of the 71 references it cites were found in a registry or an index.
Graphene Oxide Induces Toll-like Receptor 4 (TLR4)-Dependent Necrosis in Macrophages
Abstract
Graphene and graphene-based nanomaterials display novel and beneficial chemical, electrical, mechanical, and optical characteristics, which endow these nanomaterials with promising applications in a wide spectrum of areas such as electronics and biomedicine. However, its toxicity on health remains unknown and is of great concern. In the present study, we demonstrated that graphene oxide (GO) induced necrotic cell death to macrophages. This toxicity is mediated by activation of toll-like receptor 4 (TLR4) signaling and subsequently in part via autocrine TNF-α production. Inhibition of TLR4 signaling with a selective inhibitor prevented cell death nearly completely. Furthermore, TLR4-deficient bone marrow-derived macrophages were resistant to GO-triggered necrosis. Similarly, GO did not induce necrosis of HEK293T/TLR4-null cells. Macrophagic cell death upon GO treatment was partially attributed to RIP1-RIP3 complex-mediated programmed necrosis downstream of TNF-α induction. Additionally, upon uptake into macrophages, GO accumulated primarily in cytoplasm causing dramatic morphologic alterations and a significant reduction of the macrophagic ability in phagocytosis. However, macrophagic uptake of GO may not be required for induction of necrosis. GO exposure also caused a large increase of intracellular reactive oxygen species (ROS), which contributed to the cause of cell death. The combined data reveal that interaction of GO with TLR4 is the predominant molecular mechanism underlying GO-induced macrophagic necrosis; also, cytoskeletal damage and oxidative stress contribute to decreased viability and function of macrophages upon GO treatment.
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Cites
Graphene: Status and Prospects
Geim, A. K. (2009) · Science · doi:10.1126/science.1158877 · Cited by 13,942
Graphene and Graphene Oxide: Synthesis, Properties, and Applications
Zhu, Y., Murali, S., Cai, W., Li, X., Suk, J. W., Potts, J. R., & Ruoff, R. S. (2010) · Advanced Materials · doi:10.1002/adma.201001068 · Cited by 10,522
Toxic potential of materials at the nanolevel
Nel, A., Xia, T., Mädler, L., & Li, N. (2006) · Science · doi:10.1126/science.1114397 · Cited by 9,324
Self-citationDefective LPS Signaling in C3H/HeJ and C57BL/10ScCr Mice: Mutations in Tlr4 Gene
Poltorak, A., He, X., Smirnova, I., Liu, M.-Y., Huffel, C. V., Du, X., Birdwell, D., Alejos, E., Silva, M., Galanos, C., et al. (1998) · Science · doi:10.1126/science.282.5396.2085 · Cited by 7,631
Understanding biophysicochemical interactions at the nano–bio interface
Nel, A. E., Mädler, L., Velegol, D., Xia, T., Hoek, E. M. V., Somasundaran, P., Klaessig, F., Castranova, V., & Thompson, M. (2009) · Nature Materials · doi:10.1038/nmat2442 · Cited by 7,083
Self-citationRaman Spectra of Graphite Oxide and Functionalized Graphene Sheets
Kudin, K. N., Ozbas, B., Schniepp, H. C., Prud'homme, R. K., Aksay, I. A., & Car, R. (2008) · Nano Letters · doi:10.1021/nl071822y · Cited by 4,475
Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis
Nicholson, D. W., Ali, A., Thornberry, N. A., Vaillancourt, J. P., Ding, C. K., Gallant, M., Gareau, Y., Griffin, P. R., Labelle, M., Lazebnik, Y. A., et al. (1995) · Nature · doi:10.1038/376037a0 · Cited by 3,979
PEGylated Nanographene Oxide for Delivery of Water-Insoluble Cancer Drugs
Liu, Z., Robinson, J. T., Sun, X., & Dai, H. (2008) · Journal of the American Chemical Society · doi:10.1021/ja803688x · Cited by 3,589
Nano-graphene oxide for cellular imaging and drug delivery
Sun, X., Liu, Z., Welsher, K., Robinson, J. T., Goodwin, A., Zaric, S., & Dai, H. (2008) · Nano Research · doi:10.1007/s12274-008-8021-8 · Cited by 3,291
Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension
Uehata, M., Ishizaki, T., Satoh, H., Ono, T., Kawahara, T., Morishita, T., Tamakawa, H., Yamagami, K., Inui, J., Maekawa, M., et al. (1997) · Nature · doi:10.1038/40187 · Cited by 2,859
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Goenka, S., Sant, V., & Sant, S. (2014) · Journal of Controlled Release · doi:10.1016/j.jconrel.2013.10.017 · Cited by 1,311
Toxicity of graphene-family nanoparticles: a general review of the origins and mechanisms
Ou, L., Song, B., Liang, H., Liu, J., Feng, X., Deng, B., Sun, T., & Shao, L. (2016) · Particle and Fibre Toxicology · doi:10.1186/s12989-016-0168-y · Cited by 803
Gurunathan, S., & Kim, J.-H. (2016) · International Journal of Nanomedicine · doi:10.2147/ijn.s105264 · Cited by 316
Graphene oxide and reduced graphene oxide-based scaffolds in regenerative medicine
Raslan, A., Saenz del Burgo, L., Ciriza, J., & Pedraz, J. L. (2020) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2020.119226 · Cited by 258
Endotoxin Contamination in Nanomaterials Leads to the Misinterpretation of Immunosafety Results
Li, Y., Fujita, M., & Boraschi, D. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00472 · Cited by 99
Farrera, C., & Fadeel, B. (2015) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2015.03.007 · Cited by 92
Metadata
- Authors
- Qu, G., Liu, S., Zhang, S., Wang, L., Wang, X., Sun, B., Yin, N., Gao, X., Xia, T., Chen, J.-J., & Jiang, G.-B.
- Venue
- ACS Nano
- Publisher
- American Chemical Society (ACS)
- Published
- 2013-06-11
- Volume
- 7
- Issue
- 7
- Pages
- 5732-5745
- ISSN
- 1936-0851 (ISSN-L)
- 1936-086X
- OpenAlex
- W2037794305
- Cited by
- 273
- References
- 71
- FWCI
- 15.23
- Type
- journal article
- Language
- en
- Open access
- closed
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