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Amyloid fibril systems reduce, stabilize and deliver bioavailable nanosized iron

Nature Nanotechnology volume 12, pages 642–647 (2017)Cite this article

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Abstract

Iron-deficiency anaemia (IDA) is a major global public health problem1. A sustainable and cost-effective strategy to reduce IDA is iron fortification of foods2, but the most bioavailable fortificants cause adverse organoleptic changes in foods3,4. Iron nanoparticles are a promising solution in food matrices5,6,7, although their tendency to oxidize and rapidly aggregate in solution severely limits their use in fortification8. Amyloid fibrils are protein aggregates initially known for their association with neurodegenerative disorders, but recently described in the context of biological functions in living organisms9,10,11,12,13 and emerging as unique biomaterial building blocks14,15,16. Here, we show an original application for these protein fibrils as efficient carriers for iron fortification. We use biodegradable amyloid fibrils from β-lactoglobulin, an inexpensive milk protein with natural reducing effects17, as anti-oxidizing nanocarriers and colloidal stabilizers for iron nanoparticles. The resulting hybrid material forms a stable protein–iron colloidal dispersion that undergoes rapid dissolution and releases iron ions during acidic and enzymatic in vitro digestion. Importantly, this hybrid shows high in vivo iron bioavailability, equivalent to ferrous sulfate in haemoglobin-repletion and stable-isotope studies in rats, but with reduced organoleptic changes in foods. Feeding the rats with these hybrid materials did not result in abnormal iron accumulation in any organs, or changes in whole blood glutathione concentrations, inferring their primary safety. Therefore, these iron–amyloid fibril hybrids emerge as novel, highly effective delivery systems for iron in both solid and liquid matrices.

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Figure 1: Reducing effect of BLG fibrils on iron.
Figure 2: Schematic illustrations and experimental results of contrast-matching small angle neutron scattering (SANS) on iron–BLG fibril hybrid suspensions.
Figure 3: In vitro acidic/enzymatic digestion of iron–BLG fibrils characterized by TEM, SANS and EDX.
Figure 4: Animal study design, Hb changes given by Fe–FibBLG and Fe-Nano, and colour changes after fortification.

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Acknowledgements

The authors would like to thank C. Cercamondi and C. Speich for their help in the sensory studies; A. Sánchez-Ferrer (ETHZ) for discussions on the reducing effect, F. Gramm (ETHZ) for EDX detection and STEM imaging, and the support from the ETHZ Microscopy Center (ScopeM). Authors gratefully thank for their support during the animal study: E. Kemp, H. Bunnting, C. Zeder and A. Fick. We acknowledge help from C. Zeder, A. Krzystek and T. Christ for the isotope analyses. We furthermore thank L. Molinari for performing the statistical analyses and J. Lam for the assistance in the sensory experiments. N. Spencer is gratefully acknowledged for the use of the XPS spectrometer and Mr. Cossu is thanked for the technical assistance. This work was supported by the Swiss National Science Foundation, National Research Program 69, grant number 406940-144166-1.

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Author notes

  1. Yi Shen and Lidija Posavec: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Health Sciences and Technology, Laboratory of Food and Soft Materials, ETH Zurich, Schmelzbergstrasse 9, Zurich, 8092, Switzerland

    Yi Shen, Sreenath Bolisetty, Gustav Nyström & Raffaele Mezzenga

  2. Department of Health Sciences and Technology, Human Nutrition Laboratory, ETH Zurich, Schmelzbergstrasse 7, Zurich, 8092, Switzerland

    Lidija Posavec, Florentine M. Hilty & Michael B. Zimmermann

  3. Laboratory for Neutron Scattering and Imaging, PSI Paul Scherrer Institute, Villigen, 5232, Switzerland

    Joachim Kohlbrecher

  4. Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, Zurich 8057, Switzerland

    Monika Hilbe

  5. Department of Materials, Laboratory for Surface Science and Technology, ETH Zurich, Vladimir-Prelog-Weg 5, Zurich, 8093, Switzerland

    Antonella Rossi

  6. Dipartimento di Scienze Chimiche e Geologiche, Università degli Studi di Cagliari, INSTM Unit, Cittadella Universitaria di Monserrato, Cagliari, I-09100, Italy

    Antonella Rossi

  7. Centre of Excellence for Nutrition, North-West University Potchefstroom, Potchefstroom, 2531, South Africa

    Jeannine Baumgartner

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Contributions

R.M. conceived the study. Y.S. and L.P. performed the experiments. Y.S., L.P., S.B., F.M.H., J.B., M.B.Z. and R.M. designed the experiments. Y.S. produced the materials. Y.S. performed reducing effect and in vitro digestion experiments. Y.S. and G.N. imaged the material under TEM. Y.S., S.B. and J.K. performed neutron scattering experiments and analysed the data. Y.S. and A.R. performed XPS experiments and analysed the data. L.P. and Y.S. performed animal studies, data analysis and sensory performance experiments. M.H. performed histology assessments. Y.S., L.P., R.M. and M.B.Z. co-wrote the paper.

Corresponding authors

Correspondence to Michael B. Zimmermann or Raffaele Mezzenga.

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Shen, Y., Posavec, L., Bolisetty, S. et al. Amyloid fibril systems reduce, stabilize and deliver bioavailable nanosized iron. Nature Nanotech 12, 642–647 (2017). https://doi.org/10.1038/nnano.2017.58

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