Abstract
Skin protection against ultraviolet (UV) radiation is necessary to reduce sunburn damage (erythema) and has been recognized as an important preventive measure against the development of cancer. Many sun-blocking pharmaceutical products are based on titanium dioxide nanomaterials (TiO2 NMs) due to their UV barrier properties. This study aimed to assess if the UV protective efficiency of TiO2 NMs depends on their shape. We prepared TiO2 nanowires (TNW), TiO2 nanotubes (TNT), and TiO2 nanoplates (TNP) and tested their effects on human keratinocytes before and after UVB irradiation under in vitro exposure settings. The UVB radiation was applied at the dose equivalent to the UV component observed in one medial erythemal dose. The biological effects of TiO2 NMs on nonirradiated and UVB-irradiated keratinocytes were observed by means of cell viability, genotoxicity, and inflammatory response. The obtained results clearly showed that the effects of TiO2 NMs in vitro, either cytotoxic or protective, depend on their shape. These observations highlight the beneficial properties of nanomaterials that can improve the quality and efficacy of nano-enabled products only if the safe-by-design concept has been implemented during the innovation process.
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References
Baraton MI (2011) Nano-TiO2 for solar cells and photocatalytic water splitting: scientific and technological challenges for commercialization. Open Nanosci J 5:64–77. https://doi.org/10.2174/1874140101105010064
Bashir MM, Sharma MR, Werth VP (2009) TNF-α production in the skin. Arch Dermatol Res 301:87–91. https://doi.org/10.1007/s00403-008-0893-7
CIE CI de l ́Eclairage (2000) Erythema reference action spectrum and standard erythema dose. CIE ISO 171661999(E)/CIE S 007-1998, 4
Collins AR (2004) The comet assay for DNA damage and repair: principles, applications, and limitations. Mol Biotechnol 26(3):249–261. https://doi.org/10.1385/MB:26:3:249
D’Orazio J, Jarrett S, Amaro-Ortiz A, Scott T (2013) UV radiation and the skin. Int J Mol Sci 14:12222–12248. https://doi.org/10.3390/ijms140612222
Diebold U (2003) The surface science of titanium dioxide. Surf Sci Rep 43:53–229. https://doi.org/10.1016/s0167-5729(02)00100-0
Ghiazza M, Alloa E, Oliaro-Bosso S, Viola F, Livraghi S, Rembges D, Capomaccio R, Rossi F, Ponti J, Fenoglio I (2014) Inhibition of the ROS-mediated cytotoxicity and genotoxicity of nano-TiO2 toward human keratinocyte cells by iron doping. J Nanopart Res 16:2263–2217. https://doi.org/10.1007/s11051-014-2263-z
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 213:66–73. https://doi.org/10.1016/j.tox.2005.05.007
Hamilton RF, Wu N, Porter D, Buford M, Wolfarth M, Holian A (2009) Particle length-dependent titanium dioxide nanomaterials toxicity and bioactivity. Part Fibre Toxicol 6:35. https://doi.org/10.1186/1743-8977-6-35
Han X, Kuang Q, Jin M, Xie Z, Zheng L (2009) Synthesis of titania nanosheets with a high percentage of exposed (001) facets and related photocatalytic properties. J Am Chem Soc 131(9):3152–3153. https://doi.org/10.1021/ja8092373
He F, Yu W, Fan X, Jin B (2017) In vitro cytotoxicity of biosynthesized titanium dioxide nanoparticles in human prostate cancer cell lines. Trop J Pharm Res 16(12):2793–2799. https://doi.org/10.4314/tjpr.v16i12.2
Huerta-García E, Zepeda-Quiroz I, Sánchez-Barrera H, Colín-Val Z, Alfaro-Moreno E, Del M, Ramos-Godinez P, López-Marure R (2018) Molecules internalization of titanium dioxide nanoparticles is cytotoxic for H9c2 rat cardiomyoblasts. Molecules 23:1955. https://doi.org/10.3390/molecules23081955
Jin CY, Zhu BS, Wang XF, Lu QH (2008) Cytotoxicity of titanium dioxide nanoparticles in mouse fibroblast cells. Chem Res Toxicol 21:1871–1877. https://doi.org/10.1021/tx800179f
Khan M, Naqvi AH, Ahmad M (2015) Comparative study of the cytotoxic and genotoxic potentials of zinc oxide and titanium dioxide nanoparticles. Toxicol Rep 2:765–774. https://doi.org/10.1016/j.toxrep.2015.02.004
Kim Y, He YY (2014) Ultraviolet radiation-induced non-melanoma skin cancer: regulation of DNA damage repair and inflammation. Genes Dis 1(2):188–198. https://doi.org/10.1016/j.gendis.2014.08.005
Kroll A, Pillukat MH, Hahn D, Schnekenburger J (2012) Interference of engineered nanoparticles with in vitro toxicity assays. Arch Toxicol 86:1123–1136. https://doi.org/10.1007/s00204-012-0837-z
Kuchel JM, Barnetson RSC, Halliday GM (2002) Ultraviolet a augments solar-simulated ultraviolet radiation-induced local suppression of recall responses in humans. J Invest Dermatol 118:1032–1037. https://doi.org/10.1046/j.1523-1747.2002.01773.x
Lademann HJ, Weigmann Schäfer G, Müller W, Sterry JH, Jürgen Lademann PD (2000) Investigation of the stability of coated titanium microparticles used in sunscreens. Skin Pharmacol Appl Ski Physiol 13:258–264. www.karger.com/journals/sph. Accessed 6 June 2019
Li SQ, Zhu RR, Zhu H, Xue M, Sun XY, De Yao S, Wang SL (2008) Nanotoxicity of TiO2 nanoparticles to erythrocyte in vitro. Food Chem Toxicol 46:3626–3631. https://doi.org/10.1016/j.fct.2008.09.012
Long TC, Tajuba J, Sama P, Saleh N, Swartz C, Parker J, Hester S, Lowry GV, Veronesi B (2007) Nanosize titanium dioxide stimulates reactive oxygen species in brain microglia and damages neurons in vitro. Environ Health Perspect 115:1631–1637. https://doi.org/10.1289/ehp.10216
Ma Y, Guo Y, Wu S, Lv Z, Zhang Q, Ke Y (2017) Titanium dioxide nanoparticles induce size-dependent cytotoxicity and genomic DNA hypomethylation in human respiratory cells. RSC Adv 7:23560. https://doi.org/10.1039/c6ra28272e
Milić M, Leitinger G, Pavičić I, Zebić Avdičević M, Dobrović S, Goessler W, Vinković Vrček I (2015) Cellular uptake and toxicity effects of silver nanoparticles in mammalian kidney cells. J Appl Toxicol 35(6):581–592. https://doi.org/10.1002/jat.3081
Pan Z, Lee W, Slutsky L, Clark RAF, Pernodet N, Rafailovich MH (2009) Adverse effects of titanium dioxide nanoparticles on human dermal fibroblasts and how to protect cells. Small 5(4):511–520. https://doi.org/10.1002/smll.200800798
Park HO, Yu M, Kang SK, Yang SI, Kim YJ (2011) Comparison of cellular effects of titanium dioxide nanoparticles with different photocatalytic potential in human keratinocyte, HaCaT cells. Mol Cell Toxicol 7:67–75. https://doi.org/10.1007/s13273-011-0010-4
Pem B, González-Mancebo D, Moros M, Ocaña M, Becerro AI, Pavičić I, Selmani A, Babič M, Horák D, Vinković Vrček I (2018) Biocompatibility assessment of up- and down-converting nanoparticles: implications of interferences with in vitro assays. Methods Appl. Fluoresc. 7(1):014001. https://doi.org/10.1088/2050-6120/aae9c8
Petković J, Küzma T, Rade K, Novak S, Filipič M (2011a) Pre-irradiation of anatase TiO2 particles with UV enhances their cytotoxic and genotoxic potential in human hepatoma HepG2 cells. J Hazard Mater 196:145–152. https://doi.org/10.1016/j.jhazmat.2011.09.004
Petković J, Žegura B, Stevanović M, Drnovšek N, Uskoković D, Novak S, Filipič M (2011b) DNA damage and alterations in expression of DNA damage responsive genes induced by TiO2 nanoparticles in human hepatoma HepG2 cells. Nanotoxicology 5(3):341–353. https://doi.org/10.3109/17435390.2010.507316
Popov AP, Lademann J, Priezzhev AV, Myllylä R (2005) Effect of size of TiO2 nanoparticles embedded into stratum corneum on ultraviolet-A and ultraviolet-B sun-blocking properties of the skin. J Biomed Opt 10(6):064037. https://doi.org/10.1117/1.2138017
Ramkumar KM, Manjula C, Gnanakumar G, Kanjwal MA, Sekar TV, Paulmurugan R, Rajaguru P (2012) Oxidative stress-mediated cytotoxicity and apoptosis induction by TiO2 nanofibers in HeLa cells. Eur J Pharm Biopharm 81:324–333. https://doi.org/10.1016/j.ejpb.2012.02.013
Rancan F, Nazemi B, Rautenberg S, Ryll M, Hadam S, Gao Q, Hackbarth S, Haag SF, Graf C, Rühl E, Blume-Peytavi U, Lademann J, Vogt A, Meinke MC (2014) Ultraviolet radiation and nanoparticle induced intracellular free radicals generation measured in human keratinocytes by electron paramagnetic resonance spectroscopy. Skin Res Technol 20:182–193. https://doi.org/10.1111/srt.12104
Ren Y, Liu X, Geng R, Lu Q, Rao R, Tan X, Yang X, Liu W (2018) Increased level of Α2,6-sialylated glycans on HaCaT cells induced by titanium dioxide nanoparticles under UV radiation. https://doi.org/10.3390/nano8040253
Rowe RC, Sheskey PJ, Owen SC (2009) Handbook of pharmaceutical excipients, 6th edn. Pharmaceutical Press, London, pp 741–744
Selmani A, Špadina M, Plodinec M, Delač Marion I, Willinger MG, Lützenkirchen J, Gafney HD, Redel E (2015) An experimental and theoretical approach to understanding the surface properties of one-dimensional TiO2 nanomaterials. J Phys Chem C 119(34):19729–19742. https://doi.org/10.1021/acs.jpcc.5b02027
Sharma D, Parveen K, Oza A, Ledwani L (2018) Synthesis of anthraquinone-capped TiO2 nanoparticles using R. emodi roots: preparation, characterization and cytotoxic potential. Rend Lincei 48(6):594–600. https://doi.org/10.1007/s12210-018-0696-5
Sofianou MV, Trapalis C, Psycharis V, Boukos N, Vaimakis T, Yu J, Wang W (2012) Study of TiO2 anatase nano and microstructures with dominant {001} facets for NO oxidation. Environ Sci Pollut Res 19:3719–3726. https://doi.org/10.1007/s11356-012-0747-x
Sunada K, Watanabe T, Hashimoto K (2003) Studies on photokilling of bacteria on TiO2 thin film. J Photochem Photobiol A Chem 156(1–3):227–233. https://doi.org/10.1016/S1010-6030(02)00434-3
Tian F, Zhang Y, Zhang J, Pan C (2012) Raman spectroscopy: a new approach to measure the percentage of anatase TiO2 exposed (001) facets. J Phys Chem C 116(13):7515–7519. https://doi.org/10.1021/jp301256h
Vinković Vrček I, Pavičić I, Crnković T, Jurašin D, Babič M, Horák D, Lovrić M, Ferhatović L, Ćurlin M, Gajović S (2015) Does surface coating of metallic nanoparticles modulate their interference with in vitro assays? RSC Adv 5:70787. https://doi.org/10.1039/c5ra14100a
Wamer WG, Yin JJ, Wei RR (1997) Oxidative damage to nucleic acids photosensitized by titanium dioxide. Free Radic Biol Med 23(6):851–858. https://doi.org/10.1016/S0891-5849(97)00068-3
Wang Y, Cui H, Zhou J, Li F, Wang J, Chen M, Liu Q (2015) Cytotoxicity, DNA damage, and apoptosis induced by titanium dioxide nanoparticles in human non-small cell lung cancer A549 cells. Environ Sci Pollut Res 22:5519–5530. https://doi.org/10.1007/s11356-014-3717-7
Wright C, Iyer AK, Wang L, Wu N, Yakisich JS, Rojanasakul Y, Azad N (2017) Effects of titanium dioxide nanoparticles on human keratinocytes. Drug Chem Toxicol 40(1):90–100. https://doi.org/10.1080/01480545.2016.1185111
Yoshizumi M, Nakamura T, Kato M, Ishioka T, Kozawa K, Wakamatsu K, Kimura H (2008) Release of cytokines/chemokines and cell death in UVB-irradiated human keratinocytes, HaCaT. Cell Biol Int 32:1405–1411. https://doi.org/10.1016/j.cellbi.2008.08.011
Zeni PF, Dos Santos DP, Canevarolo RR, Yunes JA, Padilha FF, Júnior RLC, Egues SM, Hernández-Macedo ML (2018) Photocatalytic and cytotoxic effects of nitrogen-doped TiO2 nanoparticles on melanoma cells. J Nanosci Nanotechnol 18:3722–3728. https://doi.org/10.1166/jnn.2018.14621
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This manuscript was supported by the Croatian Science Foundation [grant number HRZZ-IP-2016-06-2436].
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Ilić, K., Selmani, A., Milić, M. et al. The shape of titanium dioxide nanomaterials modulates their protection efficacy against ultraviolet light in human skin cells. J Nanopart Res 22, 71 (2020). https://doi.org/10.1007/s11051-020-04791-0
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DOI: https://doi.org/10.1007/s11051-020-04791-0