Milk-derived peptide fibril-iron nanoparticles prepared by a coordination-driven in-situ reduction approach with high bioavailability and sustained iron (II) protection

Food Res Int. 2025 Dec;221(Pt 4):117536. doi: 10.1016/j.foodres.2025.117536. Epub 2025 Sep 19.

Abstract

Iron deficiency anemia is a worldwide public health problem that urgently needs to be addressed. Current iron supplementation is restricted by instability, gastrointestinal tract irritation, and unpleasant organoleptic changes in foods. Herein, pH-responsive fibrils assembled by milk-derived peptide EQSLVCQCLV (EV-10, β-lactoglobulin 114-123) were employed to reduce, stabilize, and improve the bioavailability of iron nanoparticles (iron NPs). EV-10 fibril‑iron nanoparticle complexes (fibril‑iron NPs) are prepared by incubating FeCl3.6H2O with fibrils at pH 2.0 and 60 °C. The fibrils reduce 71 % of iron (III) ions in-situ without external reducing agents. This process produced iron NPs that were coordinated with -COO-, -NH2, and -SH groups on fibrils. The fibril‑iron NPs remain intact and protect iron NPs under simulated gastric digestion. However, they degrade to peptide‑iron NPs after being exposed to simulated intestine digestion. The in vitro (Caco-2 cells) iron bioavailability of Fibril‑iron NPs is 1.3-folds than that of FeSO4. And, the iron concentration of fibril‑iron NPs that required to improve HGB value in vivo (IDA rats) is half that of FeSO4, which without observable cytotoxicity or pathological histological changes. Compared with FeSO4, the fibril‑iron NPs have reduced the negative effects on the sensory attributes of yogurts and fruit teas by more than 30 %. The facile preparation procedure, excellent stability, and high bioavailability of fibril‑iron NPs suggest that they have considerable potential as iron supplements for foods.

Keywords: EV-10 fibril; In-situ reduction; iron bioavailability.; iron nanoparticles; iron supplement.

MeSH terms

  • Anemia, Iron-Deficiency
  • Animals
  • Biological Availability
  • Caco-2 Cells
  • Digestion
  • Humans
  • Hydrogen-Ion Concentration
  • Iron* / chemistry
  • Iron* / pharmacokinetics
  • Lactoglobulins* / chemistry
  • Male
  • Metal Nanoparticles* / chemistry
  • Milk* / chemistry
  • Peptides* / chemistry
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Iron
  • Lactoglobulins
  • Peptides