STRUCTURE–FUNCTION DESIGN OF PROTEIN-BASED COMPLEX SYSTEMS FOR STABILIZING LACTOFERRIN AND ENHANCING IRON FORTIFICATION
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Iron fortification remains challenging due to poor solubility, rapid oxidation, and limited compatibility with complex food systems. Lactoferrin (LF), a natural iron-binding glycoprotein, offers a promising strategy for iron delivery but suffers from limited stability under processing and environmental stresses.This work systematically investigates the design of protein-based complex systems to stabilize LF and control iron behavior through interaction tuning and structural modulation. Sodium caseinate (NaCas), succinylated NaCas (S.NaCas), and alginate (Alg) were employed to construct binary and ternary systems with LF and Fe(II). By varying protein modification, component ratios, and iron concentrations, these systems enable a controlled transition from weak electrostatic complexes to highly crosslinked network structures. Results demonstrate that protein modification introduces additional negative charges, significantly strengthening electrostatic interactions and markedly improving the thermal stability of LF. In parallel, polysaccharide-mediated Fe crosslinking drives the formation of network structures that more effectively retain iron, leading to reduced iron release and suppressed oxidation. Compared to simple complexes, these networked systems provide enhanced protection for both LF and Fe under processing-relevant conditions. Furthermore, hydrogel-like structures exhibit improved performance during in vitro digestion, enabling more controlled iron release while maintaining system stability under gastrointestinal conditions. Overall, this work establishes a structure–interaction–function framework for the rational design of protein-based delivery systems for iron fortification. Preliminary scale-up exploration further suggests the feasibility of translating these systems beyond laboratory conditions. These findings provide mechanistic insights into how interaction tuning and structural control can be leveraged to develop stable, effective, and scalable nutrient delivery platforms for food applications.