Amyloid fibril systems reduce, stabilize and deliver bioavailable nanosized iron

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