Protein Cage Nanoparticles as Multifunctional Delivery Nanoplatforms

Abstract

Protein cages, including ferritins, viral capsids, and encapsulins, are biomolecule-based supramolecular polymers and attractive candidates for nano-scale cargo delivery vehicles. While the interior surfaces of the protein cages have been used for encapsulation, attachment and synthesis of organic and inorganic materials, their exterior surfaces have been used for multivalent presentations of molecules, including affinity tags, antibodies, fluorophores, carbohydrates, nucleic acids, and peptides, for molecular targeting and hierarchical structure formation. We genetically and chemically modified various types of protein cage nanoparticles to use them as multifunctional delivery nanoplatforms. Fc binding peptide and domain were genetically inserted onto the surface of protein cage nanoparticles and they formed very stable non-covalent complexes with both human and rabbit IgGs targeting specific cancer cell lines. Protein cage nanoparticles were implemented as intravascular magnetic resonance T1 contrast conjugates via site-selective attachment of Gd(III)-chelateing agents and the potential usage of Gd(III)-chelating agent-conjugated P22 capsids for in vivo MR imaging is validated by visualizing a mouse’s intravascular system. We also utilized protein cage nanoparticles as antigen-delivery nanoplatforms, and confirmed their efficacy in inducing DC-mediated antigen-specific immune responses and subsequent melanoma tumor rejection in vivo.