Hierarchical Proteinosomes for Programmed Release of Multiple Components

A facile route to hierarchically organized multi-compartmentalized proteinosomes based on a recursive Pickering emulsion procedure using amphiphilic protein-polymer nanoconjugate building blocks is described. The number of incarcerated guest proteinosomes within a single host proteinosome is controlled, and enzymes and genetic polymers encapsulated within targeted subcompartments to produce chemically organized multi-tiered structures. Three types of spatiotemporal response-retarded concomitant release, synchronous release or hierarchical release of dextran and DNA-are demonstrated based on the sequential response of the host and guest membranes to attack by protease, or through variations in the positioning of disulfide-containing cross-links in either the host or guest proteinosomes integrated into the nested architectures. Overall, our studies provide a step towards the construction of hierarchically structured synthetic protocells with chemically and spatially integrated proto-organelles.