Dissolution of 2D Molybdenum Disulfide Generates Differential Toxicity among Liver Cell Types Compared to Non-Toxic 2D Boron Nitride Effects

Jiulong Li; Linda M. Guiney; Julia R. Downing; Xiang Wang; Chong Hyun Chang; Jinhong Jiang; Qi Liu; Xiangsheng Liu; Kuo Ching Mei; Yu Pei Liao; Tiancong Ma; Huan Meng; Mark C. Hersam; André E. Nel; Tian Xia

doi:10.1002/smll.202101084

Dissolution of 2D Molybdenum Disulfide Generates Differential Toxicity among Liver Cell Types Compared to Non-Toxic 2D Boron Nitride Effects

Jiulong Li, Linda M. Guiney, Julia R. Downing, Xiang Wang, Chong Hyun Chang, Jinhong Jiang, Qi Liu, Xiangsheng Liu, Kuo Ching Mei, Yu Pei Liao, Tiancong Ma, Huan Meng, Mark C. Hersam, André E. Nel^*, Tian Xia^*

^*Corresponding author for this work

Materials Science and Engineering

Research output: Contribution to journal › Article › peer-review

22 Scopus citations

Abstract

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.

Original language	English (US)
Article number	2101084
Journal	Small
Volume	17
Issue number	25
DOIs	https://doi.org/10.1002/smll.202101084
State	Published - Jun 24 2021

Funding

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 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).

Keywords

apoptosis
boron nitride
dissolution
inflammatory response
molybdenum disulfide

ASJC Scopus subject areas

Biotechnology
General Chemistry
Biomaterials
General Materials Science
Engineering (miscellaneous)

Access to Document

10.1002/smll.202101084

Cite this

Li, J., Guiney, L. M., Downing, J. R., Wang, X., Chang, C. H., Jiang, J., Liu, Q., Liu, X., Mei, K. C., Liao, Y. P., Ma, T., Meng, H., Hersam, M. C., Nel, A. E., & Xia, T. (2021). Dissolution of 2D Molybdenum Disulfide Generates Differential Toxicity among Liver Cell Types Compared to Non-Toxic 2D Boron Nitride Effects. Small, 17(25), Article 2101084. https://doi.org/10.1002/smll.202101084

@article{a31fc4014f5e4802b617355591ace7f5,

title = "Dissolution of 2D Molybdenum Disulfide Generates Differential Toxicity among Liver Cell Types Compared to Non-Toxic 2D Boron Nitride Effects",

abstract = "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.",

keywords = "apoptosis, boron nitride, dissolution, inflammatory response, molybdenum disulfide",

author = "Jiulong Li and Guiney, {Linda M.} and Downing, {Julia R.} and Xiang Wang and Chang, {Chong Hyun} and Jinhong Jiang and Qi Liu and Xiangsheng Liu and Mei, {Kuo Ching} and Liao, {Yu Pei} and Tiancong Ma and Huan Meng and Hersam, {Mark C.} and Nel, {Andr{\'e} E.} and Tian Xia",

note = "Publisher Copyright: {\textcopyright} 2021 Wiley-VCH GmbH",

year = "2021",

month = jun,

day = "24",

doi = "10.1002/smll.202101084",

language = "English (US)",

volume = "17",

journal = "Small",

issn = "1613-6810",

publisher = "Wiley-VCH Verlag",

number = "25",

}

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

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

UR - http://www.scopus.com/inward/record.url?scp=85106327496&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85106327496&partnerID=8YFLogxK

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 -

Dissolution of 2D Molybdenum Disulfide Generates Differential Toxicity among Liver Cell Types Compared to Non-Toxic 2D Boron Nitride Effects

Abstract

Funding

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this