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Investigation of TiO2 nanoparticle interactions in the fibroblast NIH-3T3 cells via liquid-mode atomic force microscope

  • Nanotoxicology
  • Published:
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Abstract

Long before we recognized how significant they were, nanoparticles were already all around in the environment. Since then, an extensive number of synthetic nanoparticles have been engineered to improve our quality of life through rigorous scientific research on their uses in practically every industry, including semiconductor devices, food, medicine, and agriculture. The extensive usage of nanoparticles in commodities that come into proximity with human skin and internal organs through medicine has raised significant concerns over the years. TiO2 nanoparticles (NPs) are widely employed in a wide range of industries, such as cosmetics and food packaging. The interaction and internalization of TiO2 NPs in living cells have been studied by the scientific community for many years. In the present study, we investigated the cell viability, nanomechanical characteristics, and fluorescence response of NIH-3T3 cells treated with sterile DMEM TiO2 nanoparticle solution using a liquid-mode atomic force microscope and a fluorescence microscope. Two different sorts of response systems have been observed in the cells depending on the size of the NPs. TiO2 nanoparticles smaller than 100 nm support its initial stages cell viability, and cells internalize and metabolize NPs. In contrast, bigger TiO2 NPs (> 100 nm) are not completely metabolized and cannot impair cell survival. Furthermore, bigger NPs above 100 nm could not be digested by the cells, therefore hindering cell development, whereas below 100 nm TiO2 stimulated uncontrolled cell growth akin to cancerous type cells. The cytoskeleton softens as a result of particle internalization, as seen by the nanomechanical characteristics of the nanoparticle treated cells. According to our investigations, TiO2 smaller than 100 nm facilitates unintended cancer cell proliferation, whereas larger NPs ultimately suppress cell growth. Before being incorporated into commercial products, similar effects or repercussions that could result from employing different NPs should be carefully examined.

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Data availability

The data that support the findings of this study are available from the corresponding author, upon reasonable request.

References

  • Ali I, Suhail M, Alothman ZA, Alwarthan A (2018) Recent advances in syntheses, properties and applications of TiO2 nanostructures. RSC Adv 8:30125–30147

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Amiri A, Hastert FD, Heim LO, Dietz C (2020) Reliability of cancer cell elasticity in force microscopy. Appl Phys Lett 116:083701

    Article  CAS  Google Scholar 

  • Chakraborty R, Vilya K, Pradhan M, Nayak AK (2022) Recent advancement of biomass-derived porous carbon based materials for energy and environmental remediation applications. J Mater Chem A 10:6965–7005

    Article  CAS  Google Scholar 

  • Cui XG, Chen H, Ye QB, Cui XY, Cui XJ, Cui HJ, Shen GZ, Li MJ, Lin JT, Sun YX (2021) Porous titanium dioxide spheres for drug delivery and sustained release. Front Mater 8:649237

    Article  Google Scholar 

  • Dominguez R, Holmes KC (2011) Actin structure and function. Annu Rev Biophys 40:169–186

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dorier M, Beal D, Tisseyre C, Marie-Desvergne C, Dubosson M, Barreau F, Houdeau E, Herlin-Boime N, Rabilloud T, Carriere M (2019) The food additive E171 and titanium dioxide nanoparticles indirectly alter the homeostasis of human intestinal epithelial cells in vitro. Environ Sci Nano 6:1549–1561

    Article  CAS  Google Scholar 

  • Dreno B, Alexis A, Chuberre B, Marinovich M (2019) Safety of titanium dioxide nanoparticles in cosmetics. J Eur Acad Dermatol Venereol 33:34–46

    Article  CAS  PubMed  Google Scholar 

  • Dufrene YF, Ando T, Garcia R, Alsteens D, Martinez-Martin D, Engel A, Gerber C, Muller DJ (2017) Imaging modes of atomic force microscopy for application in molecular and cell biology. Nat Nanotechnol 12:295–307

    Article  CAS  PubMed  Google Scholar 

  • Eaton P, West P (2010) Atomic force microscopy. Oxford University Press, New York

    Book  Google Scholar 

  • Efremov YM, Suter DM, Timashev PS, Raman A (2022) 3D nanomechanical mapping of subcellular and sub-nuclear structures of living cells by multi-harmonic AFM with long-tip microcantilevers. Sci Rep. https://doi.org/10.1038/s41598-021-04443-w

    Article  PubMed  PubMed Central  Google Scholar 

  • Farner JM, Cheong RS, Mahe E, Anand H, Tufenkji N (2019) Comparing TiO2 nanoparticle formulations: stability and photoreactivity are key factors in acute toxicity to Daphnia magna. Environ Sci Nano 6:2532–2543

    Article  CAS  Google Scholar 

  • Fisichella M, Dabboue H, Bhattacharyya S, Lelong G, Saboungi ML, Warmont F, Midoux P, Pichon C, Guerin M, Hevor T, Salvetat JP (2010) Uptake of functionalized mesoporous silica nanoparticles by human cancer cells. J Nanosci Nanotechnol 10:2314–2324

    Article  CAS  PubMed  Google Scholar 

  • Galkina OL, Ivanov VK, Agafonov AV, Seisenbaeva GA, Kessler VG (2015) Cellulose nanofiber-titania nanocomposites as potential drug delivery systems for dermal applications. J Mater Chem B 3:1688–1698

    Article  CAS  PubMed  Google Scholar 

  • Haase K, Pelling AE (2015) Investigating cell mechanics with atomic force microscopy. J R Soc Interface 12:20140970

    Article  PubMed  PubMed Central  Google Scholar 

  • Haider AJ, Jameel ZN, Al-Hussaini IHM (2019) Review on: titanium dioxide applications. Energy Procedia 157:17–29

    Article  CAS  Google Scholar 

  • Ho MS, Kuo FJ, Lee YS, Cheng CM (2007) Atomic force microscopic observation of surface-supported human erythrocytes. Appl Phys Lett 91:015103

    Article  Google Scholar 

  • 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 22:543–553

    Article  CAS  PubMed  Google Scholar 

  • Horie M, Nishio K, Fujita K, Kato H, Endoh S, Suzuki M, Nakamura A, Miyauchi A, Kinugasa S, Yamamoto K, Iwahashi H, Murayama H, Niki E, Yoshida Y (2010) Cellular responses by stable and uniform ultrafine titanium dioxide particles in culture-medium dispersions when secondary particle size was 100 nm or less. Toxicol in Vitro 24:1629–1638

    Article  CAS  PubMed  Google Scholar 

  • Huerta-Garcia E, Marquez-Ramirez SG, Ramos-Godinez MD, Lopez-Saavedra A, Herrera LA, Parra A, Alfaro-Moreno E, Gomez EO, Lopez-Marure R (2015) Internalization of titanium dioxide nanoparticles by glial cells is given at short times and is mainly mediated by actin reorganization-dependent endocytosis. Neurotoxicology 51:27–37

    Article  CAS  PubMed  Google Scholar 

  • Huerta-Garcia E, Zepeda-Quiroz I, Sanchez-Barrera H, Colin-Val Z, Alfaro-Moreno E, Ramos-Godinez MD, Lopez-Marure R (2018) Internalization of titanium dioxide nanoparticles is cytotoxic for H9c2 rat cardiomyoblasts. Molecules 23:1955

    Article  PubMed  PubMed Central  Google Scholar 

  • Huerta-Garcia E, Ramos-Godinez MD, Lopez-Saayedra A, Alfaro-Moreno E, Gomez-Crisostomo NP, Colin-Val Z, Sanchez-Barrera H, Lopez-Marure R (2019) Internalization of titanium dioxide nanoparticles is mediated by actin-dependent reorganization and clathrin- and dynamin-mediated endocytosis in H9c2 rat cardiomyoblasts. Chem Res Toxicol 32:578–588

    Article  CAS  PubMed  Google Scholar 

  • Indumathi T, Theivarasu C, Pradeep I, Rani MT, Magesh G, Rahale CS, Kumar ER (2021) Effects of Nd doping on structural, optical, morphological and surface-chemical state analysis of ZnO nanoparticles for antimicrobial and anticancer activities. Surf Interfaces 23:1010000

    Google Scholar 

  • Ispanixtlahuatl-Meraz O, Schins RPF, Chirino YI (2018) Cell type specific cytoskeleton disruption induced by engineered nanoparticles. Environ Sci Nano 5:228–245

    Article  CAS  Google Scholar 

  • Jalalah M, Rudra S, Aljafari B, Irfan M, Almasabi SS, Alsuwian TA, Patil AAA, Nayak AK, Harraz FA (2022) Novel porous heteroatom-doped biomass activated carbon nanoflakes for efficient solid-state symmetric supercapacitor devices. J Taiwan Inst Chem Eng 132:104148

    Article  CAS  Google Scholar 

  • Kralovec K, Melounkova L, Slovakova M, Mannova N, Sedlak M, Bartacek J, Havelek R (2020) Disruption of cell adhesion and cytoskeletal networks by thiol-functionalized silica-coated iron oxide nanoparticles. Int J Mol Sci 21:9350

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Luo Q, Kuang DD, Zhang BY, Song GB (2016) Cell stiffness determined by atomic force microscopy and its correlation with cell motility. BBA-Gen Subjects 1860:1953–1960

    Article  CAS  Google Scholar 

  • Ma NN, Ma C, Li CY, Wang T, Tang YJ, Wang HY, Mou XB, Chen Z, He NY (2013) Influence of nanoparticle shape, size, and surface functionalization on cellular uptake. J Nanosci Nanotechnol 13:6485–6498

    Article  CAS  PubMed  Google Scholar 

  • Minelli E, Ciasca G, Sassun TE, Antonelli M, Palmieri V, Papi M, Maulucci G, Santoro A, Giangaspero F, Delfini R, Campi G, De Spirito M (2017) A fully-automated neural network analysis of AFM force-distance curves for cancer tissue diagnosis. Appl Phys Lett 111:143701

    Article  Google Scholar 

  • Paul CA, Kumar ER, Suryakanth J, Abd El-Rehim AF (2023) Structural, microstructural, vibrational, and thermal investigations of NiO nanoparticles for biomedical applications. Ceram Int 49:27230–27246

    Article  CAS  Google Scholar 

  • Rihane N, Nury T, M’rad I, El Mir L, Sakly M, Amara S, Lizard G (2016) Microglial cells (BV-2) internalize titanium dioxide (TiO2) nanoparticles: toxicity and cellular responses. Environ Sci Pollut Res 23:9690–9699

    Article  CAS  Google Scholar 

  • Rudra S, Janani K, Thamizharasan G, Pradhan M, Rani B, Sah NK, Nayak AK (2022) Fabrication of Mn3O4-WO3 nanoparticles based nanocomposites symmetric supercapacitor device for enhanced energy storage performance under neutral electrolyte. Electrochim Acta 406:139870

    Article  CAS  Google Scholar 

  • Sarimov RM, Nagaev EI, Matveyeva TA, Binhi VN, Burmistrov DE, Serov DA, Astashev ME, Simakin AV, Uvarov OV, Khabatova VV, Akopdzhanov AG, Schimanowskii NL, Gudkov SV (2022) Investigation of aggregation and disaggregation of self-assembling nano-sized clusters consisting of individual iron oxide nanoparticles upon interaction with HEWL protein molecules. Nanomaterials 12:3960

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Satheeshkumar MK, Kumar ER, Indhurnathi P, Srinivas C, Deepty M, Sathiyaraj S, Suriyanarayanan N, Sastry DL (2020) Structural, morphological and magnetic properties of algae/CoFe2O4 and algae/Ag-Fe-O nanocomposites and their biomedical applications. Inorg Chem Commun 111:107578

    Article  CAS  Google Scholar 

  • Shabbir S, Kulyar MF, Bhutta ZA, Boruah P, Asif M (2021) Toxicological consequences of titanium dioxide nanoparticles (TiO(2)NPs) and their jeopardy to human population. Bionanoscience 11:621–632

    Article  PubMed  PubMed Central  Google Scholar 

  • Shakeel M, Jabeen F, Shabbir S, Asghar MS, Khan MS, Chaudhry AS (2016) Toxicity of nano-titanium dioxide (TiO2-NP) through various routes of exposure: a review. Biol Trace Elem Res 172:1–36

    Article  CAS  PubMed  Google Scholar 

  • Skocaj M, Filipic M, Petkovic J, Novak S (2011) Titanium dioxide in our everyday life; is it safe? Radiol Oncol 45:227–247

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Todaro GJ, Green H (1963) Quantitative studies of the growth of mouse embryo cells in culture and their development into established lines. J Cell Biol 17:199–313

    Article  Google Scholar 

  • Treuel L, Jiang XE, Nienhaus GU (2013) New views on cellular uptake and trafficking of manufactured nanoparticles. J R Soc Interface 10:20120939

    Article  PubMed  PubMed Central  Google Scholar 

  • Younes M, Aquilina G, Castle L, Engel KH, Fowler P, Fernandez MJF, Furst P, Gundert-Remy U, Gurtler R, Husoy T, Manco M, Mennes W, Moldeus P, Passamonti S, Shah R, Waalkens-Berendsen I, Waffle D, Corsini E, Cubadda F, De Groot D, FitzGerald R, Gunnare S, Gutleb AC, Mast J, Mortensen A, Oomen A, Piersma A, Plichta V, Ulbrich B, Van Loveren H, Benford D, Bignami M, Bolognesi C, Crebelli R, Dusinska M, Marcon F, Nielsen E, Schlatter J, Vleminckx C, Barmaz S, Cart M, Civitella C, Giarola A, Rincon AM, Serafimova R, Smeraldi C, Tarazona J, Tard A, Wright M, EFSA Panel Food Additives Flavouri (2021) Safety assessment of titanium dioxide (E171) as a food additive. Efsa J 19:1

    Google Scholar 

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Acknowledgements

The authors would like to thank Dr. Duen-Yau Chuang, Department of Chemistry of National Chung Hsing University, for providing NIH-3T3 cells for this research work. In addition, the authors would like to acknowledge the financial support from the National Science and Technology Council, Taiwan (MOST-111-2112-M-005-009).

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Author notes

  1. Tz-ju Hong and Chandrasekar Sivakumar have contributed equally to this work.

Authors and Affiliations

  1. Department of Electrophysics, National Yang Ming Chiao Tung University, Hsinchu, 30010, Taiwan

    Tz-ju Hong & Chih-Wei Luo

  2. Department of Physics, National Chung Hsing University, Taichung City, 40227, Taiwan

    Chandrasekar Sivakumar & Mon-Shu Ho

  3. National Synchrotron Radiation Research Center (NSRRC), Hsinchu, 30076, Taiwan

    Chih-Wei Luo

  4. Institute of Physics and Center for Emergent Functional Matter Science, National Yang Ming Chiao Tung University, Hsinchu, 30010, Taiwan

    Chih-Wei Luo

  5. Taiwan Consortium of Emergent Crystalline Materials (TCECM), Ministry of Science and Technology, Taipei, 10601, Taiwan

    Chih-Wei Luo

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  1. Tz-ju Hong
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Contributions

TJH: methodology, experiments, investigation, software, writing—original draft. CS: methodology, investigation, writing—original draft. CWL: investigation, data curation, validation, writing—review and editing. Mon-Shu Ho: conceptualization, supervision, funding acquisition, writing—review and editing. The authors TJH and CS contributed equally to this work.

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Correspondence to Mon-Shu Ho.

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Hong, Tj., Sivakumar, C., Luo, CW. et al. Investigation of TiO2 nanoparticle interactions in the fibroblast NIH-3T3 cells via liquid-mode atomic force microscope. Arch Toxicol 97, 2893–2901 (2023). https://doi.org/10.1007/s00204-023-03585-2

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  • DOI: https://doi.org/10.1007/s00204-023-03585-2

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