UC Berkeley

Protein cage architectures such as viral capsids, heat shock proteins, and ferritins are naturally occurring nanoscale structures with exquisite homogeneity and stability. This dissertation work describes endeavors toward the use of three different protein cage architectures: the MS2 bacteriophage, a mutant of the Tobacco Mosaic Virus (TMV), and the nanophage scaffold (derived from fd phage) as therapeutic and imaging agent delivery systems. The cages were reacted with several types of organic molecules, such as drug molecules, imaging tracers, and targeting ligands. Towards the development of the platforms for therapeutic delivery, the antitumor agent doxorubicin was covalently bound on the protein scaffolds via a pH sensitive linker. The effects of these constructs on cultured mammalian cells, their biocompatibility, in vivo tumor homing and biodistribution were investigated. Tumor growth inhibition studies were also performed with these structures. Together, the results presented herein demonstrate the utility of the protein cages as robust nanoscale platforms for the delivery of cargo.