Nanoengineering of Stimuli‐Responsive Protein‐Based Biomimetic Protocells as Versatile Drug Delivery Tools

We present a general strategy to nanoengineer protein-based colloidal spheres (biomimetic protocells) as versatile delivery carriers with stimuli responsiveness by the electrostatic assembly of binary components (proteins and polypeptides) in association with intermolecular disulfide cross-linking. The size of the colloidal spheres, ranging from nanoscale to microscale, is readily tuned through parameters like protein and polypeptide concentration, the ratio between both, pH, and so on. Moreover, such colloidal spheres show versatile encapsulation of various guest molecules including small organic molecules and biomacromolecules. The pH and redox dual-responsiveness facilitates the rapid release of the payload in an acidic and reductant-enriched ambient such as in lysosomes. Thus, nanoengineering of protein-based biomimetic protocells opens a new alternative avenue for developing delivery vehicles with multifunctional properties towards a range of therapeutic and diagnostic applications.