TY - JOUR
T1 - Dissolution of 2D Molybdenum Disulfide Generates Differential Toxicity among Liver Cell Types Compared to Non-Toxic 2D Boron Nitride Effects
AU - Li, Jiulong
AU - Guiney, Linda M.
AU - Downing, Julia R.
AU - Wang, Xiang
AU - Chang, Chong Hyun
AU - Jiang, Jinhong
AU - Liu, Qi
AU - Liu, Xiangsheng
AU - Mei, Kuo Ching
AU - Liao, Yu Pei
AU - Ma, Tiancong
AU - Meng, Huan
AU - Hersam, Mark C.
AU - Nel, André E.
AU - Xia, Tian
N1 - Funding Information:
The research reported in this publication was supported by the Nanotechnology Health Implications Research (NHIR) Consortium of the National Institute of Environmental Health Sciences of the National Institutes of Health under Award Number (U01ES027237). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Cholate‐suspended BN and MoS nanosheets were procured/developed, characterized, and provided by the Engineered Nanomaterials Resource and Coordination Core established at T. H. Chan School of Public Health (NIH grant No. U24ES026946) as a service core for the Nanotechnology Health Implications Research Consortium. The authors thank the CNSI Advanced Light Microscopy/Spectroscopy and Electron Imaging Center for NanoMachines Core Facilities and the Flow Cytometry Core Facility of Jonsson Comprehensive Cancer Center at UCLA. This work made use of the Keck‐II facility of Northwestern University's NUANCE Center, which has received support from the SHyNE Resource (NSF ECCS‐1542205), the IIN, and the Northwestern University MRSEC program (NSF DMR‐1720139). 2
Funding Information:
The research reported in this publication was supported by the Nanotechnology Health Implications Research (NHIR) Consortium of the National Institute of Environmental Health Sciences of the National Institutes of Health under Award Number (U01ES027237). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Cholate-suspended BN and MoS2 nanosheets were procured/developed, characterized, and provided by the Engineered Nanomaterials Resource and Coordination Core established at T. H. Chan School of Public Health (NIH grant No. U24ES026946) as a service core for the Nanotechnology Health Implications Research Consortium. The authors thank the CNSI Advanced Light Microscopy/Spectroscopy and Electron Imaging Center for NanoMachines Core Facilities and the Flow Cytometry Core Facility of Jonsson Comprehensive Cancer Center at UCLA. This work made use of the Keck-II facility of Northwestern University's NUANCE Center, which has received support from the SHyNE Resource (NSF ECCS-1542205), the IIN, and the Northwestern University MRSEC program (NSF DMR-1720139).
Publisher Copyright:
© 2021 Wiley-VCH GmbH
PY - 2021/6/24
Y1 - 2021/6/24
N2 - 2D boron nitride (BN) and molybdenum disulfide (MoS2) materials are increasingly being used for applications due to novel chemical, electronic, and optical properties. Although generally considered biocompatible, recent data have shown that BN and MoS2 could potentially be hazardous under some biological conditions, for example, during, biodistribution of drug carriers or imaging agents to the liver. However, the effects of these 2D materials on liver cells such as Kupffer cells (KCs), liver sinusoidal endothelial cells, and hepatocytes, are unknown. Here, the toxicity of BN and MoS2, dispersed in Pluronic F87 (designated BN-PF and MoS2-PF) is compared with aggregated forms of these materials (BN-Agg and MoS2-Agg) in liver cells. MoS2 induces dose-dependent cytotoxicity in KCs, but not other cell types, while the BN derivatives are non-toxic. The effect of MoS2 could be ascribed to nanosheet dissolution and the release of hexavalent Mo, capable of inducing mitochondrial reactive oxygen species generation and caspases 3/7-mediated apoptosis in KUP5 cells. In addition, the phagocytosis of MoS2-Agg triggers an independent response pathway involving lysosomal damage, NLRP3 inflammasome activation, caspase-1 activation, IL-1β, and IL-18 production. These findings demonstrate the importance of Mo release and the state of dispersion of MoS2 in impacting KC viability.
AB - 2D boron nitride (BN) and molybdenum disulfide (MoS2) materials are increasingly being used for applications due to novel chemical, electronic, and optical properties. Although generally considered biocompatible, recent data have shown that BN and MoS2 could potentially be hazardous under some biological conditions, for example, during, biodistribution of drug carriers or imaging agents to the liver. However, the effects of these 2D materials on liver cells such as Kupffer cells (KCs), liver sinusoidal endothelial cells, and hepatocytes, are unknown. Here, the toxicity of BN and MoS2, dispersed in Pluronic F87 (designated BN-PF and MoS2-PF) is compared with aggregated forms of these materials (BN-Agg and MoS2-Agg) in liver cells. MoS2 induces dose-dependent cytotoxicity in KCs, but not other cell types, while the BN derivatives are non-toxic. The effect of MoS2 could be ascribed to nanosheet dissolution and the release of hexavalent Mo, capable of inducing mitochondrial reactive oxygen species generation and caspases 3/7-mediated apoptosis in KUP5 cells. In addition, the phagocytosis of MoS2-Agg triggers an independent response pathway involving lysosomal damage, NLRP3 inflammasome activation, caspase-1 activation, IL-1β, and IL-18 production. These findings demonstrate the importance of Mo release and the state of dispersion of MoS2 in impacting KC viability.
KW - apoptosis
KW - boron nitride
KW - dissolution
KW - inflammatory response
KW - molybdenum disulfide
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U2 - 10.1002/smll.202101084
DO - 10.1002/smll.202101084
M3 - Article
C2 - 34032006
AN - SCOPUS:85106327496
SN - 1613-6810
VL - 17
JO - Small
JF - Small
IS - 25
M1 - 2101084
ER -