Abstract
Increasing use of titanium dioxide (TiO2) nanoparticles in many commercial applications has led to emerging concerns regarding the safety and environmental impact of these materials. In this study, we have investigated the biological impact of nano-TiO2 (with particle primary size of 20 nm Aeroxide P25) on human lung cell lines in vitro and also the effect of particle size distribution on the particle uptake and apparent toxicity. The biological impact of nano-TiO2 is shown to be influenced by the concentration and particle size distribution of the TiO2 and the impact was shown to differ between the two cell lines (A549 and H1299) investigated herein. A549 cell line was shown to be relatively resistant to the total amount of TiO2 particles uptaken, as measured by cell viability and metabolic assays, while H1299 had a much higher capacity to ingest TiO2 particles and aggregates, with consequent evidence of impact at concentrations as low as 30–150 μg/mL TiO2. Evidence gathered from this study suggests that both viability and metabolic assays (measuring metabolic and mitochondrial activities and also cellular ATP level) should be carried out collectively to gain a true assessment of the impact of exposure to TiO2 particles.
Similar content being viewed by others
Abbreviations
- TiO2 :
-
Titanium dioxide
- ATP:
-
Adenosine triphosphate
- MTS:
-
[3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium
- d 90 :
-
Particle diameter at which 90% of aggregates are equal or less than that size
References
Adams LK, Lyon DY, Alvarez PJJ (2006) Comparative eco-toxicity of nanoscale TiO2, SiO2, and ZnO water suspensions. Water Res 40(19):3527–3532
AshaRani PV, Mun GLK, Hande MP, Valiyaveettil S (2009) Cytotoxicity and genotoxicity of silver nanoparticles in human cells. ACS Nano 3(2):279–290
Baggs RB, Ferin J, Oberdorster G (1997) Regression of pulmonary lesions produced by inhaled titanium dioxide in rats. Vet Pathol 34(6):592–597
Baraton MI, Merhari L (2004) Surface chemistry of TiO2 nanoparticles: influence on electrical and gas sensing properties. J Eur Ceram Soc 24(6):1399–1404
Barillet S, Simon-Deckers A, Herlin-Boime N, Mayne-L’Hermite M, Reynaud C, Cassio D, Gouget B, Carrière M (2010) Toxicological consequences of TiO2, SiC nanoparticles and multi-walled carbon nanotubes exposure in several mammalian cell types: an in vitro study. J Nanopart Res 12(1):61–73
Beydoun D, Amal R, Low G, McEvoy S (1999) Role of nanoparticles in photocatalysis. J Nanopart Res 1(4):439–458
Bickley RI, Gonzalez-Carreno T, Lees JS, Palmisano L, Tilley RJD (1991) A structural investigation of titanium dioxide photocatalysts. J Solid State Chem 92(1):178–190
Cormier SA, Lomnicki S, Backes W, Dellinger B (2006) Origin and health impacts of emissions of toxic by-products and fine particles from combustion and thermal treatment of hazardous wastes and materials. Environ Health Perspect 114(6):810–817
Ferin J, Oberdörster G, Penney DP (1992) Pulmonary retention of fine and ultrafine particles in rats. Am J Respir Cell Mol Biol 6:535–542
Friedlander S, Pui D (2004) Emerging issues in nanoparticle aerosol science and technology. J Nanopart Res 6(2):313–320
Gao H, Shi W, Freund LB (2005) Mechanics of receptor-mediated endocytosis. Proc Natl Acad Sci 102(27):9469–9474
Grassian VH, Adamcakova-Dodd A, Pettibone JM, O’Shaughnessy PT, Thorne PS (2007) Inflammatory response of mice to manufactured titanium dioxide nanoparticles: comparison of size effects through different exposure routes. Nanotoxicology 1(3):211–226
Gunawan C, Teoh WY, Marquis CP, Juniahani Lifia, Amal R (2009) Reversible antimicrobial photoswitching in nanosilver. Small 5(3):341–344
Gurr JR, Wang ASS, Chen CH, Jan KY (2005) Ultrafine titanium dioxide particles in the absence of photoactivation can induce oxidative damage to human bronchial epithelial cells. Toxicology 213(1–2):66–73
Horie M, Nishio K, Fujita K, Endoh S, Miyauchi A, Saito Y, Iwahashi H, Yamamoto K, Murayama H, Nakano H, Nanashima N, Niki E, Yoshida Y (2009) Protein adsorption of ultrafine metal oxide and its influence on cytotoxicity toward cultured cells. Chem Res Toxicol 22(3):543–553
Inoue A, Narumi K, Matsubara N, Sugawara S-i, Saijo Y, Satoh K, Nukiwa T (2000) Administration of wild-type p53 adenoviral vector synergistically enhances the cytotoxicity of anti-cancer drugs in human lung cancer cells irrespective of the status of p53 gene. Cancer Lett 157(1):105–112
Ito I, Began G, Mohiuddin I, Saeki T, Saito Y, Branch CD, Vaporciyan A, Clifton Stephens L, Yen N, Roth JA, Ramesh R (2003) Increased uptake of liposomal–DNA complexes by lung metastases following intravenous administration. Mol Ther 7(3):409–418
Jiang J, Oberdörster G, Biswas P (2009) Characterization of size, surface charge, and agglomeration state of nanoparticle dispersions for toxicological studies. J Nanopart Res 11(1):77–89
Kang SJ, Kim BM, Lee YJ, Chung HW (2008) Titanium dioxide nanoparticles trigger p53-mediated damage response in peripheral blood lymphocytes. Environ Mol Mutagen 49(5):399–405
Kho YK, Iwase A, Teoh WY, Mädler L, Kudo A, Amal R (2010) Photocatalytic H2 evolution over TiO2 nanoparticles. The synergistic effect of anatase and rutile. J Phys Chem C 114(6):2821–2829
Lam SW, Soetanto A, Amal R (2009) Self-cleaning performance of polycarbonate surfaces coated with titania nanoparticles. J Nanopart Res 11(8):1971–1979
Lee Y, Yoon S, Park M, Kim J, Lee J, Song C (2010) Influence of p53 expression on sensitivity of cancer cells to bleomycin. J Biochem Mol Toxicol 24:260–269. doi:10.1002/jbt.20334
Li J, Li Q, Xu J, Li J, Cai X, Liu R, Li Y, Ma J, Li W (2007) Comparative study on the acute pulmonary toxicity induced by 3 and 20 nm TiO2 primary particles in mice. Environ Toxicol Pharmacol 24(3):239–244
Lieber M, Todaro G, Smith B, Szakal A, Nelson-Rees W (1976) A continuous tumor-cell line from a human lung carcinoma with properties of type II alveolar epithelial cells. Int J Cancer 17(1):62–70
Liu S, Lim M, Fabris R, Chow C, Drikas M, Amal R (2008) TiO2 photocatalysis of natural organic matter in surface water: impact on trihalomethane and haloacetic acid formation potential. Environ Sci Technol 42(16):6218–6223. doi:10.1021/es800887s
Liu S, Xu L, Zhang T, Ren G, Yang Z (2010) Oxidative stress and apoptosis induced by nanosized titanium dioxide in PC12 cells. Toxicology 267(1–3):172–177
Mo Y, Lim L-Y (2005) Preparation and in vitro anticancer activity of wheat germ agglutinin (WGA)-conjugated PLGA nanoparticles loaded with paclitaxel and isopropyl myristate. J Control Release 107(1):30–42
Murdock RC, Braydich-Stolle L, Schrand AM, Schlager JJ, Hussain SM (2008) Characterization of nanomaterial dispersion in solution prior to in vitro exposure using dynamic light scattering technique. Toxicol Sci 101(2):239–253
Nohynek GJ, Lademann J, Ribaud C, Roberts MS (2007) Grey goo on the skin? Nanotechnology, cosmetic and sunscreen safety. Crit Rev Toxicol 37(3):251–277
Oberdörster G (2000) Pulmonary effects of inhaled ultrafine particles. Int Arch Occup Environ Health 74(1):1–8
Ohno T, Sarukawa K, Tokieda K, Matsumura M (2001) Morphology of a TiO2 photocatalyst (Degussa, P25) consisting of anatase and rutile cyrstalline phases. J Catal 203:82–86
Oren M (2003) Decision making by p53: life, death and cancer. Cell Death Differ 10(4):431–442
Powers KW, Brown SC, Krishna VB, Wasdo SC, Moudgil BM, Roberts SM (2006) Research strategies for safety evaluation of nanomaterials. Part VI. Characterization of nanoscale particles for toxicological evaluation. Toxicol Sci 90(2):296–303
Qian L, Hinestroza JP (2004) Application of nanotechnology for high performance textiles. J Text Appar Technol Manag 4(1):1–7
Sayes CM, Wahi R, Kurian PA, Liu Y, West JL, Ausman KD, Warheit DB, Colvin VL (2006) Correlating nanoscale titania structure with toxicity: a cytotoxicity and inflammatory response study with human dermal fibroblasts and human lung epithelial cells. Toxicol Sci 92(1):174–185
Shimamura A, Fisher DE (1996) p53 in life and death. Clin Cancer Res 2(3):435
Silverstein SC, Steinman RM, Cohn ZA (1977) Endocytosis. Annu Rev Biochem 46(1):669–722
Stearns RC, Paulauskis JD, Godleski JJ (2001) Endocytosis of ultrafine particles by A549 cells. Am J Respir Cell Mol Biol 24(2):108–115
Thevenot P, Cho J, Wavhal D, Timmons RB, Tang L (2008) Surface chemistry influences cancer killing effect of TiO2 nanoparticles. Nanomed: Nanotechnol Biol Med 4(3):226–236
Van Hoecke K, Quik JT, Mankiewicz-Boczek J, De Schamphelaere KA, Elsaesser A, Van der Meeren P, Barnes C, McKerr G, Howard CV, Van de Meent D (2009) Fate and effects of CeO2 nanoparticles in aquatic ecotoxicity tests. Environ Sci Technol 43(12):4537
Vaux D (1993) Toward an understanding of the molecular mechanisms of physiological cell death. Proc Natl Acad Sci 90(3):786–789
Wang J, Zhou G, Chen C, Yu H, Wang T, Ma Y, Jia G, Gao Y, Li B, Sun J, Li Y, Jiao F, Zhao Y, Chai Z (2007) Acute toxicity and biodistribution of different sized titanium dioxide particles in mice after oral administration. Toxicol Lett 168(2):176–185
Warheit DB, Webb TR, Sayes CM, Colvin VL, Reed KL (2006) Pulmonary instillation studies with nanoscale TiO2 rods and dots in rats: toxicity is not dependent upon particle size and surface area. Toxicol Sci 91(1):227
Warheit DB, Webb TR, Reed KL, Frerichs S, Sayes CM (2007) Pulmonary toxicity study in rats with three forms of ultrafine-TiO2 particles: differential responses related to surface properties. Toxicology 230(1):90–104
Yin Win K, Feng SS (2005) Effects of particle size and surface coating on cellular uptake of polymeric nanoparticles for oral delivery of anticancer drugs. Biomaterials 26(15):2713–2722
Young C, Lim TM, Chiang K, Scott J, Amal R (2008) Photocatalytic oxidation of toluene and trichloroethylene in the gas-phase by metallised (Pt, Ag) titanium dioxide. Appl Catal B Environ 78(1–2):1–10
Acknowledgments
The authors wish to thank Dorothy Yu and Rebeya Akter (UNSW Solid State and Elemental Analysis Unit: ICP-OES) for the quantification of TiO2 concentrations. The study was financially supported by the Australian Research Council through the ARC Centres of Excellence Program.
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Tedja, R., Marquis, C., Lim, M. et al. Biological impacts of TiO2 on human lung cell lines A549 and H1299: particle size distribution effects. J Nanopart Res 13, 3801–3813 (2011). https://doi.org/10.1007/s11051-011-0302-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11051-011-0302-6