Abstract
A safe and effective use of nanoparticles in biology and medicine requires a thorough understanding, down to the molecular level, of how nanoparticles interact with cells in the physiological environment. This study evaluated the two-way interaction between inorganic nanomaterials (INMs) and cells from A549 human lung carcinoma cell line. The interaction between silica and zinc oxide INMs and cells was investigated using both standard methods and advanced characterization techniques. The effect of INMs on cell properties was evaluated in terms of cell viability, chemical modifications, and volume changes. The effect of cells and culture medium on INMs was evaluated using dynamic light scattering (DLS), scanning electron microscopy and energy-dispersive X-ray spectroscopy (SEM–EDS), high performance liquid chromatography (HPLC), gas chromatography-mass spectroscopy (GC–MS), Fourier transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA). No cytotoxic effect was detected in the case of silicon oxide INMs, while for high doses of zinc oxide INMs a reduction of cell survival was observed. Also, increased cell volume was recorded after 24 h incubation of cells with zinc oxide INMs. A better dimensional homogeneity and colloidal stability was observed by DLS for silicon oxide INMs than for zinc oxide INMs. SEM–EDS analysis showed the effectiveness of the adopted dispersion procedure and confirmed in the case of zinc oxide INMs the presence of residual substances derived from organosilane coating. HPLC and GC–MS performed on INMs aqueous dispersions after 24 h incubation showed an additional peak related to the presence of an organic contaminant only in the case of zinc oxide INMs. FTIR Chemical Imaging carried out directly on the cells showed, in case of incubation with zinc oxide INMs, a modification of the spectra in correspondence of phospholipids, nucleic acids and proteins characteristic absorption bands when compared with untreated cells. Overall, our results confirm the importance of developing new experimental methods and techniques for improving the knowledge about the biosafety of nanomaterials.
Similar content being viewed by others
References
Peer D, Karp JM, Hong S, Farokhzad OC, Margalit R, Langer R. Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol. 2007;2:751–60.
Duncan R. Polymer conjugates as anticancer nanomedicines. Nat Rev Cancer. 2006;6:688–701.
Ferrari M. Cancer nanotechnology: opportunities and challenges. Nat Rev Cancer. 2005;5:161–71.
Zhang L, Gu FX, Chan JM, Wang AZ, Langer RS, Farokhzad OC. Nanoparticles in medicine: therapeutic applications and developments. Clin Pharm Ther. 2008;83:761–9.
Tang L, Cheng J. Nonporous silica nanoparticles for nanomedicine application. Nano Today 2013;8:290–312.
Zhang H, Xia JY, Pang X, Zhao M, Wang B, Yang L et al. Magnetic nanoparticle-loaded electrospun polymeric nanofibers for tissue engineering. Mat Sci Eng C. 2017;73:537–43.
Panchal RG. Novel therapeutic strategies to selectively kill cancer cells. Biochem Pharmacol. 1998;55:247–52.
Nel A, Xia T, Madler L, Li N. Toxic potential of materials at the nanolevel. Science. 2006;311:622–7.
McNeil SE. Nanotechnology for the biologist. J Leukoc Biol. 2005;78:585–94.
Wagner V, Dullaart A, Bock AK, Zweck A. The emerging nanomedicine landscape. Nat Biotechnol. 2006;24:1211–7.
Hanley C, Layne J, Punnoose A, Reddy KM, Coombs I, Coombs A et al. Preferential killing of cancer cells and activated human T cells using zinc oxide nanoparticles. Nanotechnology. 2008;19:295103–13.
Wang H, Wingett D, Engelhard MH, Feris K, Reddy KM, Turner P et al. Fluorescent dye encapsulated ZnO particles with cell specific toxicity for potential use in biomedical applications. J Mater Sci Mater Med. 2009;20:11–22.
Zhang Y, Nayak Y, Tapas R, Hong H, Cai W. Biomedical Applications of Zinc Oxide Nanomaterials. Curr Mol Med. 2013;13:1633–45.
Accomasso L, Cristallini C, Giachino C. Risk assessment and risk minimization in nanomedicine: a need for predictive, alternative, and 3Rs strategies. Front Pharmacol. 2018;9:art 228.
Zhang Y, Nguyen KC, Lefebvre DE, Shwed PS, Crosthwait J, Bondy GS et al. Critical experimental parameters related to the cytotoxicity of zinc oxide nanoparticles. J Nanopart Res. 2014;16:24–40.
Gojova A, Guo B, Kota RS, Rutledge JC, Kennedy IM, Barakat AI. Induction of inflammation in vascular endothelial cells by metal oxide nanoparticles: effect of particle composition. Environ Health Perspect. 2007;115:403–9.
Reddy KM, Feris K, Bell J, Wingett DG, Hanley C, Punnoose A. Selective toxicity of zinc oxide nanoparticles to prokaryotic and eukaryotic systems. Appl Phys Lett. 2007;90:2139021–3.
Gil F, Pla A, Hernandez AF, Mercado JM, Mendez F. A fatal case following exposure to zinc chloride and hexachloroethane from a smoke bomb in a fire simulation at a school. Clin Toxicol. 2008;46:563–5.
Bengalli R, Gualtieri M, Capasso L, Urani C, Camatini M. Impact of zinc oxide nanoparticles on an in vitro model of the human air-blood barrier. Toxicol Lett. 2017;279:22–32.
Sahu D, Kannan GM, Vijayaraghavan R. Size-dependent effect of zinc oxide on toxicity and inflammatory potential of human monocytes. J Toxicol Environ Health A. 2014;77:177–91.
Wang B, Zhang J, Chen C, Xu G, Qin X, Hong Y et al. The size of zinc oxide nanoparticles controls its toxicity through impairing autophagic flux in A549 lung epithelial cells. Toxicol Lett. 2018;285:51–9.
Kim I-Y, Joachim E, Choi H, Kim K. Toxicity of Silica nanoparticles depends on size, dose, and cell type. Nanomedicine. 2015;11:1407–16.
Song MK, HS Lee HS, Choi HS, Shin CY, Kim YJ, Park YK et al. Octanal-induced inflammatory responses in cells relevant for lung toxicity: expression and release of cytokines in A549 human alveolar cells. Hum Exp Toxicol. 2014;33:710–21.
Totaro S, Cotogno G, Rasmussen K, Pianella F, Roncaglia M, Olsson H et al. The JRC nanomaterials repository: a unique facility providing representative test materials for nanoEHS research. Regul Toxicol Pharmacol. 2016;81:334–40.
Miller LM, Dumas P. From structure to cellular mechanism with infrared microspectroscopy. Curr Opin Struc Biol. 2010;20:649–56.
Singh C et al. NM-series of representative manufactured nanomaterials—zinc oxide NM-110, NM-111, NM-112, NM-113: characterisation and test item preparation, Luxembourg: Publications Office of the European Union; 2011. p. 141. EUR—Scientific and Technical Research series—ISSN 1831-9424 (online), ISSN 1018-5593 (print). https://doi.org/10.2787/55008.
Rama Narsimha Reddy A, Srividya L. Evaluation of in vitro cytotoxicity of zinc oxide (ZnO) nanoparticles using human cell lines. J Toxicol Risk Assess. 2018;4:009.
Ng CT, Yong LQ, Hande, Ong CN, Yu LE, Bay BH et al. Zinc oxide nanoprtcles exhibit cytotoxicity and genotoxicity through oxidative stress responses in human lung fibroblasts and Drosophila Melanogasters. Int J Nanomed. 2017;12:1621–37.
Monopoli MP, Walczyk D, Campbell A, Elia G, Lynch I, Bombelli FB et al. Physical-chemical aspects of protein corona: relevance to in vitro and in vivo biological impacts of nanoparticles. J Am Chem Soc. 2011;133:2525–34.
Ongena K, Das C, Smith JL, Gil S, Johnston G. Determining cell number during cell culture using the Scepter cell counter. J Vis Exp. 2010;45:e2204.
Tahara M, Inoue T, Miyakura Y, Horie H, Yasuda Y, Fujii H et al. Cell diameter measurements obtained with a handheld cell counter could be used as a surrogate marker of G2/M arrest and apoptosis in colon cancer cell lines exposed to SN-38. Biochem Biophys Res Commun. 2013;434:753–9.
Varaprath S, Larson PS. Degradation of monophenylheptamethylcyclotetrasiloxane and 2,6-cis-diphenylhexamethylcycloterasiloxane in Londo Soil. J Polym Environ. 2002;10:119–31.
Varaprath S, Salyers KL, Plotzke KP, Nanavati S. Identification of metabolites of octamethilcyclotetrasiloxane (D4) in rat urine. Drug Metab Dispos. 1999;27:1267–73.
Song MK, Choi HS, Lee HS, Kim YJ, Park YK, Ryu JC. Analysis of microRNA and mRNA expression profiles highlights alterations in modulation of the MAPK pathway under octanal exposure. Environ Toxicol Pharmacol. 2014;37:84–94.
Mattson EC, Aboualizadeh E, Barabas ME, Stucky CL, Hirschmugl CJ. Opportunities for live cell FT-infrared imaging: macromolecule identification with 2D and 3D localization. Int J Mol Sci. 2013;14:22753–81.
Lipiec E, Kowalska J, Lekki J, Wiechec A, Kwiatek WM. FTIR microspectroscopy in studies of DNA damage induced by proton microbeam in single PC-3 Cells. Acta Phys Pol A. 2012;2:506–9.
Singh B, Gautam R, Kumor S, Vinaykumar BN, Nongthomba U, Nandi D et al. Application of vibrational microspectroscopy to biology and medicine. Curr Sci. 2012;102:232–44.
Falahat R, Wiranowska M, Toomeya R, Alcantar N. ATR-FTIR analysis of spectral and biochemical changes in glioma cells induced by chlorotoxin. Vib Spectrosc. 2016;87:164–72.
Mourant JR, Gibson RR, Johnson TM, Carpenter S, Short KW, Yamada YR et al. Methods for measuring the infrared spectra of biological cells. Phys Med Biol. 2003;48:243–57.
Mirzaei H, Darroudi M. Zinc oxide nanoparticles: biological synthesis and biomedical applications. Ceram Int. 2017;43:907–14.
Darroudi M, Sabouri Z, Oskuee RK, Zak AK, Kargar H, Hamid MHNA. Green chemistry approach for the synthesis of ZnO nanopowders and their cytotoxic effects. Ceram Int. 2014;40:4827–31.
Acknowledgements
This research was partially funded by the European Union Seventh Framework Programme (FP7/2007-2013) under the project NANoREG (A common European approach to the regulatory testing of nano-materials), grant agreement 310584.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Cristallini, C., Barbani, N., Bianchi, S. et al. Assessing two-way interactions between cells and inorganic nanoparticles. J Mater Sci: Mater Med 31, 1 (2020). https://doi.org/10.1007/s10856-019-6328-5
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s10856-019-6328-5