Amyloid fibril systems reduce, stabilize and deliver bioavailable nanosized iron

• Published in: Nature nanotechnology Vol. 12; no. 7; pp. 642 - 647
• Main Authors: Shen, Yi, Posavec, Lidija, Bolisetty, Sreenath, Hilty, Florentine M., Nyström, Gustav, Kohlbrecher, Joachim, Hilbe, Monika, Rossi, Antonella, Baumgartner, Jeannine, Zimmermann, Michael B., Mezzenga, Raffaele
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-07-2017; Nature Publishing Group
• Subjects: 140/146; 147/143; 147/28; 631/61/350; 631/61/54; Aggregates; Amyloid - chemistry; Amyloid - pharmacokinetics; Amyloid - pharmacology; Anemia; Anemia, Iron-Deficiency - drug therapy; Animals; Bioavailability; Biodegradability; Biodegradation; Biomaterials; Colloids; Cost engineering; Digestion; Disorders; Dissolution; Drug Delivery Systems; Feeding; Ferrous sulfate; Fibrils; Food; Food, Fortified; Glutathione; Hemoglobin; Humans; Hybrids; In vitro methods and tests; In vivo methods and tests; Iron; Iron - chemistry; Iron - pharmacokinetics; Iron - pharmacology; Iron deficiency; Iron sulfates; Isotope studies; Lactoglobulins - chemistry; Lactoglobulins - pharmacokinetics; Lactoglobulins - pharmacology; letter; Materials Science; Matrices (mathematics); Metal Nanoparticles - chemistry; Metal Nanoparticles - therapeutic use; Milk; Molecular structure; Nanoparticles; Nanotechnology; Nanotechnology and Microengineering; Neurodegenerative diseases; Nutrient deficiency; Organs; Oxidation; Proteins; Public health; Rats; Sustainability; β-Amyloid; β-Lactoglobulin
• ISSN: 1748-3387; 1748-3395
• DOI: 10.1038/nnano.2017.58

Amyloid fibrils from food-grade proteins deliver nanostructured bioavailable iron without cytotoxicity or pathological side effects.
Iron-deficiency anaemia (IDA) is a major global public health problem
1
. A sustainable and cost-effective strategy to reduce IDA is iron fortification of foods
2
, but the most bioavailable fortificants cause adverse organoleptic changes in foods
3
,
4
. Iron nanoparticles are a promising solution in food matrices
5
,
6
,
7
, although their tendency to oxidize and rapidly aggregate in solution severely limits their use in fortification
8
. Amyloid fibrils are protein aggregates initially known for their association with neurodegenerative disorders, but recently described in the context of biological functions in living organisms
9
,
10
,
11
,
12
,
13
and emerging as unique biomaterial building blocks
14
,
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 effects
17
, 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.