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Oral exposure to polystyrene nanoparticles affects iron absorption

Nature Nanotechnology volume 7, pages 264–271 (2012)Cite this article

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Abstract

The use of engineered nanoparticles in food and pharmaceuticals is expected to increase, but the impact of chronic oral exposure to nanoparticles on human health remains unknown. Here, we show that chronic and acute oral exposure to polystyrene nanoparticles can influence iron uptake and iron transport in an in vitro model of the intestinal epithelium and an in vivo chicken intestinal loop model. Intestinal cells that are exposed to high doses of nanoparticles showed increased iron transport due to nanoparticle disruption of the cell membrane. Chickens acutely exposed to carboxylated particles (50 nm in diameter) had a lower iron absorption than unexposed or chronically exposed birds. Chronic exposure caused remodelling of the intestinal villi, which increased the surface area available for iron absorption. The agreement between the in vitro and in vivo results suggests that our in vitro intestinal epithelium model is potentially useful for toxicology studies.

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Figure 1: In vitro +M cells monolayer after exposure to carboxylated polystyrene nanoparticles.
Figure 2: Particle transport experiments at 4 °C and 37 °C.
Figure 3: In vitro iron uptake and transport results after exposure to carboxylated particles.
Figure 4: In vitro iron uptake and transport results after exposure to non-ionized or aminated particles.
Figure 5: In vivo iron transport, liver ferritin, gene expression and villus volume results.

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References

  1. Sagalowicz, L. & Leser, M. E. Delivery systems for liquid food products. Curr. Opin. Colloid Interface Sci. 15, 61–72 (2010).

    Article  CAS  Google Scholar 

  2. Yoav, D. L. Milk proteins as vehicles for bioactives. Curr. Opin. Colloid Interface Sci. 15, 73–83 (2010).

    Article  Google Scholar 

  3. Edgar, A. Bioavailability of nanoparticles in nutrient and nutraceutical delivery. Curr. Opin. Colloid Interface Sci. 14, 3–15 (2009).

    Article  Google Scholar 

  4. Sozer, N. & Kokini, J. L. Nanotechnology and its applications in the food sector. Trends Biotechnol. 27, 82–89 (2009).

    Article  CAS  Google Scholar 

  5. Chaudhry, Q. et al. Applications and implications of nanotechnologies for the food sector. Food Addit. Contam. A 25, 241–258 (2008).

    Article  CAS  Google Scholar 

  6. Singh, R. & Lillard, J. W. Jr. Nanoparticle-based targeted drug delivery. Exp. Mol. Pathol. 86, 215–223 (2009).

    Article  CAS  Google Scholar 

  7. Stone, V. & Kinloch, I. Nanotoxicology: Characterization, Dosing and Health Effects (CRC, 2007).

    Google Scholar 

  8. Lomer, M. C. E., Thompson, R. P. H. & Powell, J. J. Fine and ultrafine particles of the diet: influence on the mucosal immune response and association with Crohn's disease. Proc. Nutr. Soc. 61, 123–130 (2002).

    Article  Google Scholar 

  9. Kerneis, S., Bogdanova, A., Kraehenbuhl, J. P. & Pringault, E. Conversion by Peyer's patch lymphocytes of human enterocytes into M cells that transport bacteria. Science 277, 949–952 (1997).

    Article  CAS  Google Scholar 

  10. Lomer, M. C. E., Harvey, R. S. J., Evans, S. M., Thompson, R. P. H. & Powell, J. J. Efficacy and tolerability of a low microparticle diet in a double blind, randomized, pilot study in Crohn's disease. Eur. J. Gastroenterol. Hepatol. 13, 101–106 (2001).

    Article  CAS  Google Scholar 

  11. Lomer, M. C. E. et al. Intake of dietary iron is low in patients with Crohn's disease: a case-control study. Br. J. Nutr. 91, 141–148 (2004).

    Article  CAS  Google Scholar 

  12. Lee, H. J. Protein drug oral delivery: the recent progress. Arch. Pharm. Res. 25, 572–584 (2002).

    Article  CAS  Google Scholar 

  13. Des Rieux, A., Fievez, V., Garinot, M., Schneider, Y. J. & Preat, V. Nanoparticles as potential oral delivery systems of proteins and vaccines: a mechanistic approach. J. Control. Rel. 116, 1–27 (2006).

    Article  CAS  Google Scholar 

  14. Galindo-Rodriguez, S. A., Allemann, E., Fessi, H. & Doelker, E. Polymeric nanoparticles for oral delivery of drugs and vaccines: a critical evaluation of in vivo studies. Crit. Rev. Ther. Drug. Carrier Syst. 22, 419–463 (2005).

    Article  CAS  Google Scholar 

  15. Ma, Y., Yeh, M., Yeh, K-Y. & Glass, J. Iron imports. V. Transport of iron through the intestinal epithelium. Am. J. Physiol. Gastr. L. 290, G417–G422 (2006).

    Article  CAS  Google Scholar 

  16. DeSesso, J. M. & Jacobson, C. F. Anatomical and physiological parameters affecting gastrointestinal absorption in humans and rats. Food. Chem. Toxicol. 39, 209–228 (2001).

    Article  CAS  Google Scholar 

  17. Muir, A. & Hopfer, U. Regional specificity of iron uptake by small intestinal brush-border membranes from normal and iron-deficient mice. Am. J. Physiol. Gastr. L. 248, G376–G379 (1985).

    Article  CAS  Google Scholar 

  18. Kararli, T. T. Comparison of the gastrointestinal anatomy, physiology, and biochemistry of humans and commonly used laboratory animals. Biopharm. Drug. Dispos. 16, 351–380 (1995).

    Article  CAS  Google Scholar 

  19. Sharp, D. G. & Beard, J. W. Size and density of polystyrene particles measured by ultracentrifugation. J. Biol. Chem. 185, 247–253 (1950).

    CAS  Google Scholar 

  20. Whittow, G. C. Sturkie's Avian Physiology (Academic, 2000).

    Google Scholar 

  21. Barfull, A., Garriga, C., Mitjans, M. & Planas, J. M. Ontogenetic expression and regulation of Na+-D-glucose cotransporter in jejunum of domestic chicken. Am. J. Physiol. Gastr. L. 282, G559–G564 (2002).

    Article  CAS  Google Scholar 

  22. Dahlke, F., Ribeiro, A. M. L., Kessler, A. M., Lima, A. R. & Maiorka, A. Effects of corn particle size and physical form of the diet on the gastrointestinal structures of broiler chickens. Rev. Bras. Cienc. Avic. 5, 61–67 (2003).

    Article  Google Scholar 

  23. Ojano-Dirain, C. P. et al. Determination of mitochondrial function and site-specific defects in electron transport in duodenal mitochondria in broilers with low and high feed efficiency. Poultry Sci. 83, 1394–1403 (2004).

    Article  CAS  Google Scholar 

  24. Miles, R. D., Butcher, G. D., Henry, P. R. & Littell, R. C. Effect of antibiotic growth promoters on broiler performance, intestinal growth parameters, and quantitative morphology. Poultry Sci. 85, 476–485 (2006).

    Article  CAS  Google Scholar 

  25. Klasing, K. C. Avian gastrointestinal anatomy and physiology. Semin. Avian Exot. Pet 8, 42–50 (1999).

    Article  Google Scholar 

  26. Hidalgo, I. J., Raub, T. J. & Borchardt, R. T. Characterization of the human-colon carcinoma cell-line (Caco-2) as a model system for intestinal epithelial permeability. Gastroenterology 96, 736–749 (1989).

    Article  CAS  Google Scholar 

  27. Lesuffleur, T., Barbat, A., Dussaulx, E. & Zweibaum, A. Growth adaptation to methotrexate of HT-29 human colon-carcinoma cells is associated with their ability to differentiate into columnar absorptive and mucus-secreting cells. Cancer Res. 50, 6334–6343 (1990).

    CAS  Google Scholar 

  28. Mahler, G. J., Shuler, M. L. & Glahn, R. P. Characterization of Caco-2 and HT29-MTX cocultures in an in vitro digestion/cell culture model used to predict iron bioavailability. J. Nutr. Biochem. 20, 494–502 (2009).

    Article  CAS  Google Scholar 

  29. Schulte, R. et al. Translocation of Yersinia enterocolitica across reconstituted intestinal epithelial monolayers is triggered by Yersinia invasin binding to β1 integrins apically expressed on M-like cells. Cell Microbiol. 2, 173–185 (2000).

    Article  CAS  Google Scholar 

  30. Giannasca, P. J., Giannasca, K. T., Leichtner, A. M. & Neutra, M. R. Human intestinal M cells display the sialyl Lewis A antigen. Infect. Immun. 67, 946–953 (1999).

    CAS  Google Scholar 

  31. Owen, R. L. & Ermak, T. H. Structural specializations for antigen uptake and processing in the digestive-tract. Springer Semin. Immun. 12, 139–152 (1990).

    Article  CAS  Google Scholar 

  32. Narai, A., Arai, S. & Shimizu, M. Rapid decrease in transepithelial electrical resistance of human intestinal Caco-2 cell monolayers by cytotoxic membrane perturbents. Toxicol. In Vitro 11, 347–351 (1997).

    Article  CAS  Google Scholar 

  33. Ranaldi, G., Marigliano, I., Vespignani, I., Perozzi, G. & Sambuy, Y. The effect of chitosan and other polycations on tight junction permeability in the human intestinal Caco-2 cell line. J. Nutr. Biochem. 13, 157–167 (2002).

    Article  CAS  Google Scholar 

  34. Menard, S., Cerf-Bensussan, N. & Heyman, M. Multiple facets of intestinal permeability and epithelial handling of dietary antigens. Mucosal Immunol. 3, 247–259 (2010).

    Article  CAS  Google Scholar 

  35. Söderholm, J. D. et al. Increased epithelial uptake of protein antigens in the ileum of Crohn's disease mediated by tumour necrosis factor α. Gut 53, 1817–1824 (2004).

    Article  Google Scholar 

  36. Tako, E., Rutzke, M. A. & Glahn, R. P. Using the domestic chicken (Gallus gallus) as an in vivo model for iron bioavailability. Poultry Sci. 89, 514–521 (2010).

    Article  CAS  Google Scholar 

  37. Tako, E. & Glahn, R. P. White beans provide more bioavailable iron than red beans: Studies in poultry (Gallus gallus) and an in vitro digestion/Caco-2 model. Int. J. Vitam. Nutr. Res. 80, 416–429 (2010).

    Article  CAS  Google Scholar 

  38. Passaniti, A. & Roth, T. F. Purification of chicken liver ferritin by two novel methods and structural comparison with horse spleen ferritin. Biochem. J. 258, 413–419 (1989).

    Article  CAS  Google Scholar 

  39. Mete, A. et al. Partial purification and characterization of ferritin from the liver and intestinal mucosa of chickens, turtledoves and mynahs. Avian Pathol. 34, 430–434 (2005).

    Article  CAS  Google Scholar 

  40. Tako, E., Ferket, P. R. & Uni, Z. Changes in chicken intestinal zinc exporter mRNA expression and small intestinal functionality following intra-amniotic zinc-methionine administration. J. Nutr. Biochem. 16, 339–346 (2005).

    Article  CAS  Google Scholar 

  41. Smirnov, A., Tako, E., Ferket, P. R. & Uni, Z. Mucin gene expression and mucin content in the chicken intestinal goblet cells are affected by in ovo feeding of carbohydrates. Poultry Sci. 85, 669–673 (2006).

    Article  CAS  Google Scholar 

  42. Caspary, W. F. Physiology and pathophysiology of intestinal absorption. Am. J. Clin. Nutr. 55, 299S–308S (1992).

    Article  CAS  Google Scholar 

  43. Pluske, J. R. et al. Maintenance of villus height and crypt depth, and enhancement of disaccharide digestion and monosaccharide absorption, in piglets fed on cows’ whole milk after weaning. Br. J. Nutr. 76, 409–422 (1996).

    Article  CAS  Google Scholar 

  44. Tarachai, P. & Yamauchi, K. Effects of luminal nutrient absorption, intraluminal physical stimulation, and intravenous parenteral alimentation on the recovery responses of duodenal villus morphology following feed withdrawal in chickens. Poultry Sci. 79, 1578–1585 (2000).

    Article  CAS  Google Scholar 

  45. Basu, T. K. & Donaldson, D. Intestinal absorption in health and disease: micronutrients. Best Pract. Res. Clin. Gastroenterol. 17, 957–979 (2003).

    Article  CAS  Google Scholar 

  46. Hilty, F. M. et al. Iron from nanocompounds containing iron and zinc is highly bioavailable in rats without tissue accumulation. Nature Nanotech. 5, 374–380 (2010).

    Article  CAS  Google Scholar 

  47. NRC. Nutrient Requirements of Poultry 9th edn (National Academy Press, 1994).

Download references

Acknowledgements

The authors acknowledge financial support from the National Science Foundation for the Nanobiotechnology Center at Cornell University (ECS-9876771), the New York State Office of Science, Technology and Academic Research (for a Distinguished Professorship for M.L.S.), the Army Corp of Engineers (ID W9132T-07-2-0010) and the US Department of Agriculture. The HT29-MTX cell line was kindly contributed by Thécla Lesuffleur (INSERM U560).

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Authors and Affiliations

  1. Department of Bioengineering, Binghamton University, Binghamton, 13902, New York, USA

    Gretchen J. Mahler

  2. Department of Biomedical Engineering, Cornell University, Ithaca, 14853, New York, USA

    Mandy B. Esch, Shivaun D. Archer & Michael L. Shuler

  3. US Department of Agriculture, Plant, Soil and Nutrition Laboratory, Agricultural Research Services, Tower Road, Ithaca, 14853, New York, USA

    Elad Tako & Raymond P. Glahn

  4. Department of Biomedical Sciences, Cornell University, Ithaca, 14853, New York, USA

    Teresa L. Southard

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Contributions

G.J.M., M.B.E., S.D.A., R.P.G. and M.L.S. conceived and designed the experiments. G.J.M. performed the in vitro studies. G.J.M., M.B.E. and E.T. handled the chickens daily and E.T. and R.P.G. performed the chicken surgery. E.T. performed the microbiological analysis and M.B.E. prepared the histological samples. T.L.S. analysed the histology samples. G.J.M., M.B.E. and E.T. analysed the data. All authors co-wrote the paper.

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Correspondence to Michael L. Shuler.

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The authors declare no competing financial interests.

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Mahler, G., Esch, M., Tako, E. et al. Oral exposure to polystyrene nanoparticles affects iron absorption. Nature Nanotech 7, 264–271 (2012). https://doi.org/10.1038/nnano.2012.3

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