Development of protein cages for active encapsulation and cellular delivery of biomolecules and drugs

Abstract

In order to efficiently deliver a biomolecule to a target cell, a compartmentalized internal cavity that can protect the delivery material from the external environment is required. In vivo, a complex hierarchical structure is formed to construct a physical barrier using lipids, polysaccharides and proteins. Such various biomaterials are being developed as a delivery platform capable of performing a specific function through genetic or chemical modification, and used for diagnosis and treatment of diseases. In particular, among nano-sized structures, cage proteins have low toxicity, high solubility, and ideal size for endocytosis. The cage protein forms a delivery structure through a specific interaction with cargos. Most of the encapsulation strategy require disassembly process, binding to the cargos and then reassembling to form a complete cage. In this process, a loss of cage protein may occur and the efficiency of drug or biomaterial loading may be lowered, which can be viewed as a disadvantage of a protein-based delivery system. Therefore, in this study, Archaeoglobus fulgidus ferritin (AfFtn) derived from archaea and mi3 cage protein implemented by computational protein design were engineered to encapsulate biomolecules by simple mixing rather than goes through the process of disassembly/reassembly. A protein cage delivery system capable of active and selective encapsulation has been developed.