Structurally Programmable Dual-Compartment Ferritin Nanocarrier for Coordinated Iron and Zinc Supplementation

Abstract

Iron and zinc deficiencies often co-occur in infants and young children, but single supplementation is limited by poor bioavailability. Guided by AlphaFold3 (AF3) structural prediction, a linear cysteine-based motif was introduced to engineer the ferritin intrasubunit interface, enabling the construction of a dual-compartment nanocarrier capable of segregated Fe and Zn loading. In the engineered GKFN3C variant, a dual-compartment metal-binding architecture was successfully established at the subunit interface, enabling Zn2+ enrichment within the interfacial region without interfering with the oxidative mineralization and deposition of Fe2+ in the inner cavity. Compared with GKFN, GKFN3C showed significantly enhanced metal loading, with Zn and Fe increasing from 193 ± 9 to 239 ± 13 and from 334 ± 6 to 474 ± 23 ions per cage, respectively. This work provides a structurally programmable and efficiency-enhanced nanodesign strategy for coordinated multimineral supplementation.