Development of Theranostic Nanoplatforms using Various Protein Architectures

Abstract

Theranostics means simultaneous integration of therapeutics and diagnostics. As the material sciences and nanotechnology have significantly evolved, nanoscale novel platforms for biomedical applications become a critical issue owing to their beneficial nano-sized ranges, including quantum effects, large surface area, and enhanced bioavailability. So far, numerous theranostic platforms of synthetic organic or/and inorganic nanoparticles have been robustly developed. But, they could have inherent complexity and heterogeneity, leading to relatively difficult to precisely control their physical and chemical properties such as size, shape, composition and morphology. One of the promising candidates used in theranostics is a biocompatible protein produced by the nature’s bio-systems. The protein has a highly uniform size distribution with well-organized structures on the basis of the atomic resolution crystal structures. Also, this information makes it possible to easily impart the desired functionality to the target sites by rational design. Besides, the proteins possess molecular plasticity that can allow multiple genetic and chemical modifications. Thus, the protein architectures have a tremendous potential to be excellent biomaterials in theranostics. In this thesis, the studies on developing theranostic nanoplatforms using various forms of protein architectures would be reported. Among numerous protein architectures, protein cages are attractive candidates in that they are naturally assembled from multiple copies of identical subunits with the various diameters. Therefore, relatively large P22 viral capsids whose outer diameters are 64 nm and small lumazine synthase that are produced from Aquifex aeolicus protein cage nanoparticles with outer diameters of 15.4 nm have been used to develop as modular targeted delivery nanotemplates for theranostic agents. Going beyond, another protein architecture, monomeric fusion protein (GST_Z), was developed to apply a novel affinity protein that can have the cooperative binding ability to the various forms of antibodies. Using the GST_Z as a targeting ligand, the limitations that the antibodies have, such as low flexibility can be fixed and advantages of antibodies’ high affinity and specificity can be used by complexation between the antibodies and the GST_Z without employing any chemistry. Moreover, the GST_Z was displayed as targeting ligands outside highly stable polymeric nanoparticles via thiol-disulfide exchange reactions. This new hybrid form can also serve as a theranostic platform that integrates multiple functions, cell targeting, imaging and therapy. In sum, representatively two forms of protein architectures have been developed as theranostic nanoplatforms and their efficacy were examined using various biochemical and biophysical methods.