Hierarchical cage-protein assemblies for protein-based cellular drug delivery

Abstract

Ferritin, an iron storage protein with a spherical cage structure, has extensively studied as a protein-based drug delivery carrier because it can load diverse small drug molecules into the cavity and specifically target tumor cells. However, the pharmacokinetic limitations caused by the small size of the monomer cage, as well as the unclear loading method, not only make universal drug applicability difficult, but also result in a low loading rate, which needs to be improved. To overcome the limitations of small vehicles in previous studies, high-order ferritin and ferritin-coated nano-droplet particles were developed in this paper as universal biomolecule carriers with controllable size. The self-limited higher-order ferritins fabricated with partial surface activation of ferritin demonstrated enhanced intracellular uptake due to the synergistic effect of the targeting derived from its multivalent properties. Furthermore, protein nano-droplet particles with a narrow size distribution of several hundred nanometers were fabricated by coating the surface of biomolecular condensate with high-order ferritin. It was possible to load macro biomolecules such as nucleic acids and proteins in a stable way. It is expected that by developing a new concept platform that precisely and stably fabricates the size-controllable carrier with target drugs at high density, it will be used as a universal delivery system that can respond to requirements that vary depending on the delivery environment or purpose, such as immunotherapy or gene therapy.