Mechanisms of Iron Uptake from Ferric Phosphate Nanoparticles in Human Intestinal Caco-2 Cells

Abstract

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.

Iron nanoparticle bio-interactions evaluated in Xenopus laevis embryos, a model for studying the safety of ingested nanoparticles

“…While the different pathways involved in the absorption of various iron species in duodenal enterocytes are well-documented (Blanco-Rojo and Vaquero 2019), the mechanisms by which iron NPs are internalized are less consolidated since the pathway is conditioned by the physico-chemical properties of NPs such as size and charge. Considering the size, endocytosis is the canonical pathway feasible for iron NPs (Perfecto et al 2017), while when the permeability of the tight junctions between enterocytes is increased, NPs less than 50 nm in diameter pass through the paracellular route (Jahn et al 2012). However, based on transport and TEM studies in Caco-2 cells, a mechanism of diffusion across enterocyte plasma membrane has been hypothesized for FeO NPs with a neutral hydrophilic shell (Jahn et al 2012).…”

Ferric Citrate Supplementation Reduces Red‐Blood‐Cell Aggregation and Improves CD163+ Macrophage‐Mediated Hemoglobin Metabolism in a Rat Model of High‐Fat‐Diet‐Induced Obesity

“…Therefore, all forms of iron can likely modulate RBC function, and the iron modulatory effects observed in our study are not caused by the presence of citrate in ferric iron. However, iron absorption is extremely complex, and nutritional iron biochemistry was only partially understood till now . Further research is warranted to clarify the potential role of iron as a therapeutic agent for abnormal RBC function in obese individuals.…”

Co‐products of beef processing enhance non‐haem iron absorption in an in vitro digestion/caco‐2 cell model

“…(). An adapted model, where digests are applied directly to caco‐2 cells (Andre et al ., ; Pongrac et al ., ; Perfecto et al ., ) was used in our experiments. Twenty‐four hours before each uptake experiment, DMEM was replaced with Minimum Essential Medium (MEM, M4655) with 1% NEAA but without FBS.…”