A Novel Bacterioferritin-Based Platform for Iron Supplementation via Integrated Delivery of Heme and Non-heme Iron

Abstract Iron supplementation strategies generally rely on either heme or nonheme iron, whereas systems capable of integrating both forms within a single carrier remain scarce. Here, Escherichia coli bacterioferritin (EcBFR), which naturally binds up to 12 heme molecules through Met52 at the 2-fold symmetry axis, was investigated as a dual-iron delivery platform. EcBFR exhibited excellent thermal stability, maintaining saturated heme binding, structural integrity, and oligomeric assembly after heat treatment. It accommodated up to approximately 800 Fe atoms per nanocage, forming a predominantly ferrihydrite mineral core without compromising its structural integrity. In a Caco-2 cell model, EcBFR-mediated iron delivery resulted in significantly greater cellular iron uptake than that of free heme or ferrous sulfate.