Interfacial‐Design Mediated Construction of Hybrid Multicompartment Architectures with Layered Physicochemical Barriers for Separately Sequestration of Oxidation–Reduction Molecules and Their Redox Reaction Regulation

Abstract Hybrid multicompartment artificial architectures, inherited from different compartmental systems, possess separate microenvironments that can perform different functions. Herein, a hybrid compartmentalized architecture via hybridizing ferritin nanocage (Fn) with non‐aqueous droplets using aminated‐modified amphiphilic gelatin (AGEL) is proposed, which enables the generation of compartmentalized emulsions with hybrid multicompartments. The resulting compartmentalized emulsions are termed “hybrasome”. Specifically, by chemically attaching ethylenediamine to gelatin, the programmed noncovalent docking of Fn‐AGEL nanoparticles is implemented and their interfacial self‐rearrangement generates hybrasome with layered physicochemical barriers. Confocal Laser Scanning Microscopy images show that Fn nanocages are deposited on the non‐aqueous droplets, separated by gelatin layers. Interfacial adsorption kinetics reveal that lower permeation and rearrangement rates of Fn are responsible for their double‐layered structure formation. By choosing oxidized iron nanoparticles and reductant carnosic acid (CA) as models, these two molecules are co‐encapsulated separately within the hybrasome, resulting in significant inhibition of the redox reaction. After structural destruction in the intestine, a redox reaction is triggered and leads to the Fe 2+ redox products release, which generates a suitable valence state of iron element for cell absorption. Overall, this approach may open up an avenue for facile construction of hybrid compartmentalized architectures used to co‐encapsulate incompatible compounds separately and control the sequential release of targeted components.