Abstract
Nanotechnology is increasingly developing area including more than 700 commercial products such as clothing, food preparation, cosmetics, mechanics, electronics and also health industry. People generally contact with nanoparticles by inhaling from air. Thus, it is becoming important issue to understand harmful effects of nanoparticles on human health and prepare risk reports for common nano-sized materials. In this paper, synthesis, characterization and cytotoxicity evaluation of boron nitride (BN) nanoparticles were performed on human primary alveolar epithelial cells (HPAEpiC) since, main exposure to nanoparticles would generally happen through lung via inhalation. Chemically synthetized BN nanoparticles were characterized by using X-ray crystallography, transmission electron microscope, scanning electron microscope and energy-dispersive X-ray spectroscopy techniques. 3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide, neutral red and lactate dehydrogenase release assays were used to analyze cytotoxicity after nanoparticles exposure. Whole genome microarray analysis was used to find out the effects of BN NPs on gene expressions of HPAEpiC cells. Finally, the database for annotation, visualization and integrated discovery analysis was used to reveal relationships between different cellular pathways and nanoparticle exposure. According to cytotoxicity analysis LC20 value for BN nanoparticles was 125.051 mg/L. Microarray results showed that 2159 genes expression change (FC ≥ 2) significantly over 40,000 genes analysis. When the gene pathways were analyzed, it was seemed that BN nanoparticles mostly affect cell cycle, cell–cell interactions, cancer affecting genes and signal transduction. In a conclusion, our results supported for the first time that BN nanoparticles could be used as a safe nanomaterial in both pharmacological and medical applications.
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Ahmad P, Khandaker MU, Amin YM (2015) Synthesis of boron nitride nanotubes by argon supported thermal chemical vapor deposition. Phys E Low Dimens Syst Nanostruct 67:33–37. https://doi.org/10.1016/j.physe.2014.11.003
Brown DM, Wilson MR, MacNee W et al (2001) Size-dependent proinflammatory effects of ultrafine polystyrene particles: a role for surface area and oxidative stress in the enhanced activity of ultrafines. Toxicol Appl Pharmacol 175:191–199. https://doi.org/10.1006/taap.2001.9240
Bulera SJ, Eddy SM, Ferguson E et al (2001) RNA expression in the early characterization of hepatotoxicants in Wistar rats by high-density DNA microarrays. Hepatology 33:1239–1258. https://doi.org/10.1053/jhep.2001.23560
Chen X, Wu P, Rousseas M et al (2009) Boron nitride nanotubes are noncytotoxic and can be functionalized for interaction with proteins and cells. J Am Chem Soc 131:890–891. https://doi.org/10.1021/ja807334b
Ciofani G, Raffa V, Menciassi A, Cuschieri A (2008a) Cytocompatibility, interactions, and uptake of polyethyleneimine-coated boron nitride nanotubes by living cells: confirmation of their potential for biomedical applications. Biotechnol Bioeng 101:850–858. https://doi.org/10.1002/bit.21952
Ciofani G, Raffa V, Menciassi A, Dario P (2008b) Preparation of boron nitride nanotubes aqueous dispersions for biological applications. J Nanosci Nanotechnol 8:6223–6231. https://doi.org/10.1166/jnn.2008.339
Ciofani G, Danti S, Genchi GG et al (2012) Pilot in vivo toxicological investigation of boron nitride nanotubes. Int J Nanomed 7:19–24
Duan X, Gao Y, Yang H et al (2015) Polymorphisms in the DUSP10 gene are associated with sex-specific colorectal cancer risk in a Han population. Int J Clin Exp Pathol 8:2018–2025
Engler M, Lesniak C, Damasch R et al (2007) Hexagonal boron nitride (hBN): applications from metallurgy to cosmetics. CFI Ceram Forum Int 84:49–53
Hardman R (2006) A toxicologic review of quantum dots: toxicity depends on physicochemical and environmental factors. Environ Health Perspect 114:165–172
Horváth L, Magrez A, Golberg D et al (2011) In vitro investigation of the cellular toxicity of boron nitride nanotubes. ACS Nano 5:3800–3810. https://doi.org/10.1021/nn200139h
Karim MZ, Cameron DC, Murphy MJ, Hashmi MSJ (1991) Plasma deposition of cubic boron nitride films from non-toxic material at low temperatures. Surf Coat Technol 49:416–421. https://doi.org/10.1016/0257-8972(91)90093-C
Kasar RR, Deshpande NG, Gudage YG et al (2008) Studies and correlation among the structural, optical and electrical parameters of spray-deposited tin oxide (SnO2) thin films with different substrate temperatures. Phys B Condens Matter 403:3724–3729
Kim T, Kim K, Lee SH et al (2009) Identification of LRRc17 as a negative regulator of receptor activator of NF-kappaB ligand (RANKL)-induced osteoclast differentiation. J Biol Chem 284:15308–15316. https://doi.org/10.1074/jbc.M807722200
Lee JR, Lee MH, Eo HJ et al (2014) The contribution of activating transcription factor 3 to apoptosis of human colorectal cancer cells by protocatechualdehyde, a naturally occurring phenolic compound. Arch Biochem Biophys 564:203–210. https://doi.org/10.1016/j.abb.2014.10.005
Lewinski N, Colvin V, Drezek R (2008) Cytotoxicity of nanoparticles. Small 4:26–49. https://doi.org/10.1002/smll.200700595
Lim SY, Yuzhalin AE, Gordon-Weeks AN, Muschel RJ (2016) Targeting the CCL2–CCR2 signaling axis in cancer metastasis. Oncotarget 7: 28697–28710. https://doi.org/10.18632/oncotarget.7376
Luo H, Shao Y, Yao N et al (2015) Association of heme oxygenase-1 polymorphisms with cancer risk: a systematic review and meta-analysis. J BUON 20:1142–1153.
Lv W, Lin Y, Song W et al (2014) Variants of COL3A1 are associated with the risk of stroke recurrence and prognosis in the Chinese population: a prospective study. J Mol Neurosci 53:196–203. https://doi.org/10.1007/s12031-014-0283-x
Nair S, Muller YL, Ortega E et al (2012) Association analyses of variants in the DIO2 gene with early-onset type 2 diabetes mellitus in Pima Indians. Thyroid 22:80–87. https://doi.org/10.1089/thy.2010.0455
Noonan EJ, Place RF, Giardina C, Hightower LE (2007) Hsp70B’ regulation and function. Cell Stress Chaperones 12:393–402
Oberdörster G, Stone V, Donaldson K (2009) Toxicology of nanoparticles: a historical perspective. Nanotoxicology 1: 2-25. https://doi.org/10.1080/17435390701314761.
Paine RT, Narula CK (1990) Synthetic routes to boron nitride. Chem Rev 90:73–91. https://doi.org/10.1021/cr00099a004
Reilly TP, Bourdi M, Brady JN et al (2001) Expression profiling of acetaminophen liver toxicity in mice using microarray technology. Biochem Biophys Res Commun 282:321–328. https://doi.org/10.1006/bbrc.2001.4576
Singh S, Nalwa HS (2007) Nanotechnology and health safety–toxicity and risk assessments of nanostructured materials on human health. J Nanosci Nanotechnol 7:3048–3070. https://doi.org/10.1166/jnn.2007.922
Smith MW, Jordan KC, Park C et al (2009) Very long single- and few-walled boron nitride nanotubes via the pressurized vapor/condenser method. Nanotechnology 20:505604. https://doi.org/10.1088/0957-4484/20/50/505604
Sousa A, Sousa EMB (2006) Influence of synthesis temperature on the structural characteristics of mesoporous silica. J Non Cryst Solids 352:3451–3456. https://doi.org/10.1016/j.jnoncrysol.2006.03.080
Tsoncheva T, Rosenholm J, Teixeira CV et al (2006) Preparation, characterization and catalytic behavior in methanol decomposition of nanosized iron oxide particles within large pore ordered mesoporous silicas. Microporous Mesoporous Mater 89:209–218. https://doi.org/10.1016/j.micromeso.2005.10.028
Turkez H, Geyikoglu F, Mokhtar YI, Togar B (2012) Eicosapentaenoic acid protects against 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced hepatic toxicity in cultured rat hepatocytes. Cytotechnology. https://doi.org/10.1007/s10616-011-9386-1
Turkez H, Sönmez E, Di Stefano A, Mokhtar YI (2016) Health risk assessments of lithium titanate nanoparticles in rat liver cell model for its safe applications in nanopharmacology and nanomedicine. Cytotechnology 68:291–302. https://doi.org/10.1007/s10616-014-9780-6
Waring JF, Gum R, Morfitt D et al (2002) Identifying toxic mechanisms using DNA microarrays: evidence that an experimental inhibitor of cell adhesion molecule expression signals through the aryl hydrocarbon nuclear receptor. Toxicology 181–182:537–550. https://doi.org/10.1016/S0300-483X(02)00477-8
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This research was supported by National Boron Research Institute (BOREN) (Grant Number: Ç0391).
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Türkez, H., Arslan, M.E., Sönmez, E. et al. Synthesis, characterization and cytotoxicity of boron nitride nanoparticles: emphasis on toxicogenomics. Cytotechnology 71, 351–361 (2019). https://doi.org/10.1007/s10616-019-00292-8
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DOI: https://doi.org/10.1007/s10616-019-00292-8