Mechanisms of iron uptake from ferric phosphate nanoparticles in human intestinal Caco-2 cells

Antonio Perfecto, Christine Elgy, Eugenia Valsami-Jones, Paul Sharp, Florentine Hilty, Susan Fairweather-Tait*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)
95 Downloads (Pure)


Food fortification programs to reduce iron deficiency anemia require bioavailable forms of iron that do not cause adverse organoleptic effects. Rodent studies show that nano-sized ferric phosphate (NP-FePO4) is as bioavailable as ferrous sulfate, but there is controversy over the mechanism of absorption. We undertook in vitro studies to examine this using a Caco-2 cell model and simulated gastrointestinal (GI) digestion. Supernatant iron concentrations increased inversely with pH, and iron uptake into Caco-2 cells was 2–3 fold higher when NP-FePO4 was digested at pH 1 compared to pH 2. The size and distribution of NP-FePO4 particles during GI digestion was examined using transmission electron microscopy. The d50 of the particle distribution was 413 nm. Using disc centrifugal sedimentation, a high degree of agglomeration in NP-FePO4 following simulated GI digestion was observed, with only 20% of the particles ≤1000 nm. In Caco-2 cells, divalent metal transporter-1 (DMT1) and endocytosis inhibitors demonstrated that NP-FePO4 was mainly absorbed via DMT1. Small particles may be absorbed by clathrin-mediated endocytosis and micropinocytosis. These findings should be considered when assessing the potential of iron nanoparticles for food fortification.

Original languageEnglish
Article number359
Issue number4
Publication statusPublished - 4 Apr 2017


  • Bioavailability
  • Caco-2 cells
  • DMT1
  • Endocytosis
  • Nano iron
  • NP-FePO4
  • Simulated gastrointestinal digestion


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