journal article·2016-11

Nanosilica induced dose-dependent cytotoxicity and cell type-dependent multinucleation in HepG2 and L-02 cells

Yongbo Yu, Junchao Duan, Yang Li, Yang Yu, Hejing Hu, Jing Wu, Yannan Zhang, Yanbo Li, CaixiaGuo, Xianqing Zhou, Zhiwei Sun

Journal of Nanoparticle Research· Volume 18· Issue 11
Publisher page

Abstract

The prevalent exposure to nanosilica gained concerns about health effects of these particles on human beings. Although nanosilica-induced multinucleation has been confirmed previously, the underlying mechanism was still not clear; this study was to investigate the origination of multinucleated cells caused by nanosilica (62 nm) in both HepG2 and L-02 cells. Cell viability and cellular uptake was determined by MTT assay and transmission electron microscope (TEM), respectively. Giemsa staining was applied to detect multinucleation. To clarify the origination of multinucleated cells, fluorescent probes, PKH26 and PKH67, time-lapse observation were further conducted by confocal microscopy. Results indicated that nanosilica particles were internalized into cells and induced cytotoxicity in a dose-dependent manner. Quantification analysis showed that nanosilica significantly increased the rates of binucleated and multinucleated cells, which suggested mitotic catastrophe induction. Moreover, dynamic visualization verified that multinucleation resulted from cell fusion in HepG2 cells not in L-02 cells after nanosilica exposure, suggesting cell type-dependent multinucleation formation. Both multinucleation and cell fusion were involved in genetic instability, which emphasized the significance to explore the multinucleation induced by nanosilica via environmental, occupational and consumer product exposure.
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Research context

OpenAlex topics: Nanoparticles: synthesis and applications · Nanoparticle-Based Drug Delivery · Arsenic contamination and mitigation

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

References (57)

Show source-provided references
1. Beddoes CM, Case CP, Briscoe WH (2015) Understanding nanoparticle cellular entry: a physicochemical perspective. Adv Colloid Interf Sci 218:48–6810.1016/j.cis.2015.01.007 ↗
2. Chen EH, Grote E, Mohler W, Vignery A (2007) Cell-cell fusion. FEBS Lett 581:2181–219310.1016/j.febslet.2007.03.033 ↗
3. Chen Q, Xue Y, Sun J (2013) Kupffer cell-mediated hepatic injury induced by silica nanoparticles in vitro and in vivo. Int J Nanomedicine 8:1129–1140
4. Chu Z, Huang Y, Tao Q, Li Q (2011) Cellular uptake, evolution, and excretion of silica nanoparticles in human cells. Nanoscale 3:3291–329910.1039/c1nr10499c ↗
5. Couto S, Griffey S, Duarte P, Madewell B (2002) Feline vaccine-associated fibrosarcoma: morphologic distinctions. Veterinary Pathology Online 39:33–4110.1354/vp.39-1-33 ↗
6. Dekkers S et al (2011) Presence and risks of nanosilica in food products. Nanotoxicology 5:393–40510.3109/17435390.2010.519836 ↗
7. Dinicola S et al (2015) Multiwalled carbon nanotube buckypaper induces cell cycle arrest and apoptosis in human leukemia cell lines through modulation of AKT and MAPK signaling pathways. Toxicol in Vitro 29:1298–130810.1016/j.tiv.2015.05.006 ↗
8. Dittmar T, Zanker KS (2015) Tissue regeneration in the chronically inflamed tumor environment: implications for cell fusion driven tumor progression and therapy resistant tumor hybrid cells. Int J Mol Sci 16:30362–3038110.3390/ijms161226240 ↗
9. Downs TR et al (2012) Silica nanoparticles administered at the maximum tolerated dose induce genotoxic effects through an inflammatory reaction while gold nanoparticles do not. Mutat Res-Genet Toxicol Environ Mutag 745:38–5010.1016/j.mrgentox.2012.03.012 ↗
10. Du Z et al (2013) Cardiovascular toxicity of different sizes amorphous silica nanoparticles in rats after intratracheal instillation. Cardiovasc Toxicol 13:194–20710.1007/s12012-013-9198-y ↗
11. Duan J et al (2013a) Toxic effect of silica nanoparticles on endothelial cells through DNA damage response via Chk1-dependent G2/M checkpoint. PLoS One 8:e62087
12. Duan JC, Yu YB, Li Y, Yu Y, Sun ZW (2013b) Cardiovascular toxicity evaluation of silica nanoparticles in endothelial cells and zebrafish model. Biomaterials 34:5853–586210.1016/j.biomaterials.2013.04.032 ↗
13. Fruijtier-Pölloth C (2012) The toxicological mode of action and the safety of synthetic amorphous silica—a nanostructured material. Toxicology 294:61–7910.1016/j.tox.2012.02.001 ↗
14. Galluzzi L et al (2012) Molecular definitions of cell death subroutines: recommendations of the nomenclature committee on cell death 2012. Cell Death Differ 19:107–12010.1038/cdd.2011.96 ↗
15. Gonzalez L et al (2010) Exploring the aneugenic and clastogenic potential in the nanosize range: A549 human lung carcinoma cells and amorphous monodisperse silica nanoparticles as models. Nanotoxicology 4:382–39510.3109/17435390.2010.501913 ↗
16. Guichard Y et al (2015) Genotoxicity of synthetic amorphous silica nanoparticles in rats following short-term exposure. Part 2: intratracheal instillation and intravenous injection. Environ Mol Mutagen 56:228–24410.1002/em.21928 ↗
17. Hao N, Li L, Tang F (2014) Shape-mediated biological effects of mesoporous silica nanoparticles. J Biomed Nanotechnol 10:2508–253810.1166/jbn.2014.1940 ↗
18. Horvath L et al (2011) In vitro investigation of the cellular toxicity of boron nitride nanotubes. ACS Nano 5:3800–381010.1021/nn200139h ↗
19. International Agency for Research on Cancer (IARC) (1997) Silica, some silicates, coal dust and para-aramid 7fibrils: IARC monographs on the evaluation of the carcinogenic risks on humans. World Health Organization
20. Kang SJ, Lee YJ, Lee EK, Kwak MK (2012) Silver nanoparticles-mediated G2/M cycle arrest of renal epithelial cells is associated with NRF2-GSH signaling. Toxicol Lett 211:334–34110.1016/j.toxlet.2012.04.016 ↗
21. Khalid H, Mukherjee SP, O’Neill L, Byrne HJ (2016) Structural dependence of in vitro cytotoxicity, oxidative stress and uptake mechanisms of poly(propylene imine) dendritic nanoparticles. J Appl Toxicol 36:464–47310.1002/jat.3267 ↗
22. Kroemer G et al (2009) Classification of cell death: recommendations of the nomenclature committee on cell death 2009. Cell Death Differ 16:3–1110.1038/cdd.2008.150 ↗
23. Kumar CG, Poornachandra Y, Chandrasekhar C (2015) Green synthesis of bacterial mediated anti-proliferative gold nanoparticles: inducing mitotic arrest (G2/M phase) and apoptosis (intrinsic pathway). Nanoscale 7:18738–1875010.1039/C5NR04577K ↗
24. Le Bihan O et al (2009) Cryo-electron tomography of nanoparticle transmigration into liposome. J Struct Biol 168:419–42510.1016/j.jsb.2009.07.006 ↗
25. Li Y et al (2015) Cytoskeleton and chromosome damage leading to abnormal mitosis were involved in multinucleated cells induced by silicon nanoparticles. Part Part Syst Charact 32:636–64510.1002/ppsc.201400180 ↗
26. Li Y et al (2011) Size-dependent cytotoxicity of amorphous silica nanoparticles in human hepatoma HepG2 cells. Toxicol in Vitro 25:1343–135210.1016/j.tiv.2011.05.003 ↗
27. Lu X et al (2011) In vitro cytotoxicity and induction of apoptosis by silica nanoparticles in human HepG2 hepatoma cells. Int J Nanomedicine 6:1889
28. Madl AK, Plummer LE, Carosino C, Pinkerton KE (2014) Nanoparticles, lung injury, and the role of oxidant stress. Annu Rev Physiol 76:447–46510.1146/annurev-physiol-030212-183735 ↗
29. Mamaeva V, Sahlgren C, Linden M (2013) Mesoporous silica nanoparticles in medicine-recent advances. Adv Drug Del Rev 65:689–70210.1016/j.addr.2012.07.018 ↗
30. Mu QS, Hondow NS, Krzeminski L, Brown AP, Jeuken LJC, Routledge MN (2012) Mechanism of cellular uptake of genotoxic silica nanoparticles. Part Fibre Toxicol 9(29):1–1110.1186/1743-8977-9-29 ↗
31. Napierska D, Thomassen L, Lison D, Martens JA, Hoet PH (2010) The nanosilica hazard: another variable entity. Part Fibre Toxicol 7:3910.1186/1743-8977-7-39 ↗
32. Nishimori H, Kondoh M, Isoda K, S-i T, Tsutsumi Y, Yagi K (2009) Silica nanoparticles as hepatotoxicants. Eur J Pharm Biopharm 72:496–50110.1016/j.ejpb.2009.02.005 ↗
33. Ogle BM, Cascalho M, Platt JL (2005) Biological implications of cell fusion. Nat Rev Mol Cell Biol 6:567–57510.1038/nrm1678 ↗
34. Pawelek JM (2005) Tumour-cell fusion as a source of myeloid traits in cancer. Lancet Oncol 6:988–99310.1016/S1470-2045(05)70466-6 ↗
35. Pawelek JM, Chakraborty AK (2008) The cancer cell-leukocyte fusion theory of metastasis. Adv Cancer Res 101(101):397–44410.1016/S0065-230X(08)00410-7 ↗
36. Phillips E et al. (2014) Clinical translation of an ultrasmall inorganic optical-PET imaging nanoparticle probe. Sci Transl Med 6(260):1–910.1126/scitranslmed.3009524 ↗
37. Roiter Y, Ornatska M, Rammohan AR, Balakrishnan J, Heine DR, Minko S (2008) Interaction of nanoparticles with lipid membrane. Nano Lett 8:941–94410.1021/nl080080l ↗
38. Talebi AR, Khorsandi L, Moridian M (2013) The effect of zinc oxide nanoparticles on mouse spermatogenesis. J Assist Reprod Genet 30:1203–120910.1007/s10815-013-0078-y ↗
39. Tang F, Li L, Chen D (2012) Mesoporous silica nanoparticles: synthesis, biocompatibility and drug delivery. Adv Mater 24:1504–153410.1002/adma.201104763 ↗
40. Tarantini A et al (2015a) Genotoxicity of synthetic amorphous silica nanoparticles in rats following short-term exposure. Part 1: oral route. Environ Mol Mutagen 56:218–22710.1002/em.21935 ↗
41. Tarantini A et al (2015b) Toxicity, genotoxicity and proinflammatory effects of amorphous nanosilica in the human intestinal Caco-2 cell line. Toxicol in Vitro 29:398–40710.1016/j.tiv.2014.10.023 ↗
42. Vranic S et al (2013) Deciphering the mechanisms of cellular uptake of engineered nanoparticles by accurate evaluation of internalization using imaging flow cytometry. Part Fibre Toxicol 10:210.1186/1743-8977-10-2 ↗
43. Wang SF et al (2014) The role of autophagy in the neurotoxicity of cationic PAMAM dendrimers. Biomaterials 35:7588–759710.1016/j.biomaterials.2014.05.029 ↗
44. Wang W et al (2013) Multinucleation and cell dysfunction induced by amorphous silica nanoparticles in an L-02 human hepatic cell line. Int J Nanomedicine 8:3533
45. Wang Y et al (2015) Mesoporous silica nanoparticles in drug delivery and biomedical applications. Nanomedicine 11:313–32710.1016/j.nano.2014.09.014 ↗
46. Wu J, Wang C, Sun J, Xue Y (2011) Neurotoxicity of silica nanoparticles: brain localization and dopaminergic neurons damage pathways. ACS Nano 5:4476–448910.1021/nn103530b ↗
47. Xie G, Sun J, Zhong G, Shi L, Zhang D (2010) Biodistribution and toxicity of intravenously administered silica nanoparticles in mice. Arch Toxicol 84:183–19010.1007/s00204-009-0488-x ↗
48. Yanes RE et al (2013) Involvement of lysosomal exocytosis in the excretion of mesoporous silica nanoparticles and enhancement of the drug delivery effect by exocytosis inhibition. Small 9:697–70410.1002/smll.201201811 ↗
49. Yoshida K, Obata S, Ono M, Esaki M, Maejima T, Sawada H (2007) TPA-induced multinucleation of a mesenchymal stem cell-like clone is mediated primarily by karyokinesis without cytokinesis, although cell–cell fusion also occurs. Eur J Cell Biol 86:461–47110.1016/j.ejcb.2007.04.003 ↗
50. Yu C et al (2015a) In depth analysis of apoptosis induced by silica coated manganese oxide nanoparticles in vitro. J Hazard Mater 283:519–52810.1016/j.jhazmat.2014.09.060 ↗
51. Yu Y et al (2015b) Aberrant cytokinesis and cell fusion result in multinucleation in HepG2 cells exposed to silica nanoparticles. Chem Res Toxicol 28:490–50010.1021/tx500473h ↗
52. Yu Y et al (2014a) Silica nanoparticles induce autophagy and autophagic cell death in HepG2 cells triggered by reactive oxygen species. J Hazard Mater 270:176–18610.1016/j.jhazmat.2014.01.028 ↗
53. Yu Y et al (2013) Acute toxicity of amorphous silica nanoparticles in intravenously exposed ICR mice. PLoS One 8:e61346
54. Yu YB et al (2014b) Silica nanoparticles induce autophagy and autophagic cell death in HepG2 cells triggered by reactive oxygen species. J Hazard Mater 270:176–18610.1016/j.jhazmat.2014.01.028 ↗
55. Zhang T, Wang L, Chen Q, Chen C (2014) Cytotoxic potential of silver nanoparticles. Yonsei Med J 55:283–29110.3349/ymj.2014.55.2.283 ↗
56. Zhou X, Merchak K, Lee W, Grande JP, Cascalho M, Platt JL (2015) Cell fusion connects oncogenesis with tumor evolution. Am J Pathol 185:2049–206010.1016/j.ajpath.2015.03.014 ↗
57. Zhu J et al (2013) Size-dependent cellular uptake efficiency, mechanism, and cytotoxicity of silica nanoparticles toward HeLa cells. Talanta 107:408–41510.1016/j.talanta.2013.01.037 ↗