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Viability and gene expression responses to polymeric nanoparticles in human and rat cells

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Abstract

Applications of polymeric nanoparticles (NP) in medical fields are rapidly expanding. However, the influence of polymeric NP on cell growth and functions is widely underestimated. Therefore, we have studied cell and polymeric NP interactions by addressing two cell types with two endpoints (viability and gene expressions). Rat NR8383 and human THP-1 monocytic cell lines were exposed to 6 to 200 μg/mL of Eudragit® RL NP for 24 h, and cellular viability was estimated using MTT, WST-1, and trypan blue tests. A decrease of viability was observed with NR8383 cells (down to 70 % for 200 μg/mL), and on the contrary, an increase with THP-1 cells (up to 140 % for 200 μg/mL). Differential expression of genes involved in oxidative damage (NCF1), inflammation (NFKB, TNFA, IL6, IL1B), autophagy (ATG16L), and apoptotic balance (PDCD4, BCL2, CASP8) was analyzed. ATG16L, BCL2, and TNFA were up-regulated in NR8383 cells, which are consistent with an induction of autophagy and inflammation. On the other hand, NCF1, NFKB, and IL1B were down-regulated in THP-1 cells, which may contribute to explain the increase of cellular viability. Our results show that (1) the toxic potency of NP is dependent on the cellular model used and (2) mechanistic toxicology should be the corner stone for the evaluation of NP hazard.

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References

  • Bhattacharjee S, Ershov D, Fytianos K, van der Gucht J, Alink GM, Rietjens IMCM, et al. Cytotoxicity and cellular uptake of tri-block copolymer nanoparticles with different size and surface characteristics. Part Fibre Toxicol. 2012;30:9.

    Google Scholar 

  • Bhattacharjee S, Ershov D, van der Gucht J, Alink GM, Rietjens IMCM, Zuilhof H, et al. Surface charge-specific cytotoxicity and cellular uptake of tri-block copolymer nanoparticles. Nanotoxicology. 2013;7(1):71–84.

    Article  CAS  PubMed  Google Scholar 

  • Bodmeier R, Chen H, Tyle P, Jarosz P. Spontaneous formation of drug-containing acrylic nanoparticles. J Microencapsul. 1991;8(2):161–70.

    Article  CAS  PubMed  Google Scholar 

  • Claude JR, members of Afssaps Working Party. Recommendations for toxicological evaluation of nanoparticle medicinal Products. In: Cartwright AC, Matthews BR, editors. International Pharmaceutical Product Registration. Boca Raton: CRC Press; 2009. p. 755–61.

  • Cui WJ, Li JR, Zhang YK, Rong HL, Lu WS, Jiang L. Effects of aggregation and the surface properties of gold nanoparticles on cytotoxicity and cell growth. Nanomedicine. 2012;8(1):46–53.

    Article  CAS  PubMed  Google Scholar 

  • De Stefano D, Carnuccio R, Maiuri MC. Nanomaterials toxicity and cell death modalities. J Drug Deliv. 2012;2012:167896.

    Article  PubMed Central  PubMed  Google Scholar 

  • Eidi H, Joubert O, Attik G, Duval RE, Bottin MC, Hamouia A, et al. Cytotoxicity assessment of heparin nanoparticles in NR8383 macrophages. Int J Pharm. 2010;396(1–2):156–65.

    Article  CAS  PubMed  Google Scholar 

  • Eidi H, Joubert O, Nemos C, Grandemange S, Mograbi B, Foliguet B, et al. Drug delivery by polymeric nanoparticles induces autophagy in macrophages. Int J Pharm. 2012;422(1–2):495–503.

    Article  CAS  PubMed  Google Scholar 

  • Hayashi Y, Engelmann P, Foldbjerg R, Szabo M, Somogyi I, Pollak E, et al. Earthworms and humans in vitro: characterizing evolutionarily conserved stress and immune responses to silver nanoparticles. Environ Sci Technol. 2012;46(7):4166–73.

    Article  CAS  PubMed  Google Scholar 

  • Hussien R, Rihn BH, Eidi H, Ronzani C, Joubert O, Ferrari L, et al. Unique growth pattern of human mammary epithelial cells induced by polymeric nanoparticles. Physiol rep. 2013;1(4):e00027.

    Article  PubMed Central  PubMed  Google Scholar 

  • Jiao Y, Ubrich N, Marchand-Arvier M, Vigneron C, Hoffman M, Lecompte T, et al. In vitro and in vivo evaluation of oral heparin-loaded polymeric nanoparticles in rabbits. Circulation. 2002;105(2):230–5.

    Article  CAS  PubMed  Google Scholar 

  • Kumari A, Yadav SK, Yadav SC. Biodegradable polymeric nanoparticles based drug delivery systems. Colloids Surf B: Biointerfaces. 2010;75(1):1–18.

    Article  CAS  PubMed  Google Scholar 

  • Lanone S, Rogerieux F, Geys J, Dupont A, Maillot-Marechal E, Boczkowski J, et al. Comparative toxicity of 24 manufactured nanoparticles in human alveolar epithelial and macrophage cell lines. Part Fibre Toxicol. 2009;6:14.

    Article  PubMed Central  PubMed  Google Scholar 

  • Luo S, Rubinsztein DC. Atg5 and Bcl-2 provide novel insights into the interplay between apoptosis and autophagy. Cell Death Differ. 2007;14:1247–50.

    Article  CAS  PubMed  Google Scholar 

  • Ma XW, Wu YY, Jin SB, Tian Y, Zhang XN, Zhao YL, et al. Gold nanoparticles induce autophagosome accumulation through size-dependent nanoparticle uptake and lysosome impairment. ACS Nano. 2011;5(11):8629–39.

    Article  CAS  PubMed  Google Scholar 

  • Monopoli MP, Åberg C, Salvati A, Dawson KA. Biomolecular coronas provide the biological identity of nanosized materials. Nat Nanotechnol. 2012;7(12):779–86.

    Article  CAS  PubMed  Google Scholar 

  • National Research Council (US) Committee on Applications of Toxicogenomic Technologies to Predictive Toxicology. Applications of toxicogenomic technologies to predictive toxicology and risk assessment. Washington (DC): National Academies (US); 2007.

    Google Scholar 

  • Nel A, Xia T, Madler L, Li N. Toxic potential of materials at the nanolevel. Science. 2006;311(5761):622–7.

    Article  CAS  PubMed  Google Scholar 

  • Ngwa HA, Kanthasamy A, Gu Y, Fang N, Anantharam V, Kanthasamy AG. Manganese nanoparticle activates mitochondrial dependent apoptotic signaling and autophagy in dopaminergic neuronal cells. Toxicol Appl Pharmacol. 2011;256(3):227–40.

    Article  PubMed Central  Google Scholar 

  • Niu J, Wang K, Kolattukudy PE. Cerium oxide nanoparticles inhibit oxidative stress and nuclear factor-kappaB activation in H9c2 cardiomyocytes exposed to cigarette smoke extract. J Pharmacol Exp Ther. 2011;338(1):53–61.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Oberdorster G, Oberdorster E, Oberdorster J. Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ Health Perspect. 2005;113(7):823–39.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Peirson SN, Butler JN, Foster RG. Experimental validation of novel and conventional approaches to quantitative real-time PCR data analysis. Nucleic Acids Res. 2003;31(14):e73.

    Article  PubMed Central  PubMed  Google Scholar 

  • Pignatello R, Bucolo C, Puglisi G. Ocular tolerability of Eudragit RS100 (R) and RL1009 (R) nanosuspensions as carriers for ophthalmic controlled drug delivery. J Pharm Sci. 2002;91(12):2636–41.

    Article  CAS  PubMed  Google Scholar 

  • Scherbart AM, Langer J, Bushmelev A, van Berlo D, Haberzettl P, van Schooten FJ, et al. Contrasting macrophage activation by fine and ultrafine titanium dioxide particles is associated with different uptake mechanisms. Part Fibre Toxicol. 2011;13:8.

    Google Scholar 

  • Shimizu S, Kanaseki T, Mizushima N, Mizuta T, Arakawa-Kobayashi S, Thompson CB, et al. Role of Bcl-2 family proteins in a non-apoptotic programmed cell death dependent on autophagy genes. Nat Cell Biol. 2004;6:1221–8.

    Article  CAS  PubMed  Google Scholar 

  • Stone V, Donaldson K. Nanotoxicology—signs of stress. Nat Nanotechnol. 2006;1(1):23–4.

    Article  CAS  PubMed  Google Scholar 

  • Sze A, Erickson D, Ren LQ, Li DQ. Zeta-potential measurement using the Smoluchowski equation and the slope of the current-time relationship in electroosmotic flow. J Colloid Interface Sci. 2003;261(2):402–10.

    Article  CAS  PubMed  Google Scholar 

  • Ubrich N, Schmidt C, Bodmeier R, Hoffman M, Maincent P. Oral evaluation in rabbits of cyclosporin-loaded Eudragit RS or RL nanoparticles. Int J Pharm. 2005;288(1):169–75.

    Article  CAS  PubMed  Google Scholar 

  • van der Ploeg MJ, van den Berg JH, Bhattacharjee S, de Haan LH, Ershov DS, Fokkink RG, et al. In vitro nanoparticle toxicity to rat alveolar cells and coelomocytes from the earthworm Lumbricus rubellus. Nanotoxicology. 2014;8(1):28–37.

    Article  PubMed  Google Scholar 

  • Wagner AJ, Bleckmann CA, Murdock RC, Schrand AM, Schlager JJ, Hussain SM. Cellular interaction of different forms of aluminum nanoparticles in rat alveolar macrophages. J Phys Chem B. 2007;111(25):7353–9.

    Article  CAS  PubMed  Google Scholar 

  • Wu Y, Yang WL, Wang CC, Hu JH, Fu SK. Chitosan nanoparticles as a novel delivery system for ammonium glycyrrhizinate. Int J Pharm. 2005;295(1–2):235–45.

    Article  CAS  PubMed  Google Scholar 

  • Xia T, Kovochich M, Liong M, Zink JI, Nel AE. Cationic polystyrene nanosphere toxicity depends on cell-specific endocytic and mitochondrial injury pathways. ACS Nano. 2008;2(1):85–96.

    Article  CAS  PubMed  Google Scholar 

  • Xiong SJ, George S, Yu HY, Damoiseaux R, France B, Ng KW, et al. Size influences the cytotoxicity of poly (lactic-co-glycolic acid) (PLGA) and titanium dioxide (TiO2) nanoparticles. Arch Toxicol. 2013;87(6):1075–86.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the Agence Nationale de la Recherche (ANR NanoSNO). Ramia Safar is the recipient of a PhD grant from the Ministry of Higher Education of Syria.

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The authors declare no conflict of interest.

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Authors and Affiliations

  1. Faculté de Pharmacie, EA 3452 CITHÉFOR, Université de Lorraine, 5 rue Albert Lebrun, 54000, Nancy, France

    Carole Ronzani, Ramia Safar, Roudayna Diab, Alain Le Faou, Bertrand H. Rihn & Olivier Joubert

  2. Faculté de Médecine, Service Commun de Microscopie, Université de Lorraine, Nancy, France

    Jérôme Chevrier & Justine Paoli

  3. Faculté de Médecine de Nancy, Université de Lorraine, Nancy, France

    Alain Le Faou

  4. Food Toxicology & Contaminants, Department National Research Center, Cairo, Egypt

    Mosaad A. Abdel-Wahhab

Authors
  1. Carole Ronzani
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  2. Ramia Safar
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  3. Roudayna Diab
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  4. Jérôme Chevrier
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  5. Justine Paoli
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  6. Mosaad A. Abdel-Wahhab
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  7. Alain Le Faou
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  8. Bertrand H. Rihn
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  9. Olivier Joubert
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Corresponding author

Correspondence to Olivier Joubert.

Additional information

Ronzani Carole and Safar Ramia contributed equally to this work.

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Ronzani, C., Safar, R., Diab, R. et al. Viability and gene expression responses to polymeric nanoparticles in human and rat cells. Cell Biol Toxicol 30, 137–146 (2014). https://doi.org/10.1007/s10565-014-9275-4

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  • DOI: https://doi.org/10.1007/s10565-014-9275-4

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