A novel calcium supplement prepared by phytoferritin nanocages protects against absorption inhibitors through a unique pathway.

The consumption of milk is declining in industrialized countries, leading to inadequate calcium intake. Therefore, it is important to explore a new class of Ca-enriched nutrient for the fortification of food. In this work, we prepared a novel class of soluble and edible Ca-protein complexes where approximately 140 calcium ions were encapsulated within a phytoferritin nanocage. As an alternative to other organic and/or inorganic carriers, protein nanocages were found to provide a unique vehicle of biological origin for the intracellular delivery of calcium ions for supplementation. Such encapsulation can protect calcium ions within protein cages against dietary factors such as tannic acid (TA), oxalic acid (OA), and other divalent metal ions in foodstuffs. We demonstrated that the calcium-containing ferritin composites can be absorbed by Caco-2 cells through a process where a TfR1 receptor is involved, whereas the uptake of free calcium ions has been known to be associated with another receptor, DMT1, indicating that the calcium ions encapsulated in supramolecular protein cages can be internalized by the Caco-2 cells through a different pathway from its free analogs for calcium supplementation.