| Drug delivery and imaging are two central areas of biomedical research. In both applications, vesicles are needed to transport and deliver drugs or contrast agents to sites of interest via the circulatory system. Protein microspheres can be used to achieve these goals. These microspheres are core-shell vesicles that have a non-aqueous core and a shell made of albumin molecules cross-linked via inter-protein disulfide bonds. They are generated by sonicating a two-phase system consisting of a vegetable oil phase and an aqueous albumin phase. These vesicles have been employed in imaging modalities such as ultrasound imaging, magnetic resonance imaging (MRI), and computer assisted tomography (CT). Despite these imaging applications, the protein microspheres have limitations that have precluded their use in a wide range of other biomedical applications.; In this thesis, I have developed methods to systematically modify the core, shell, and surface of the protein microspheres. In addition, I have shown that the size of these spheres can be reduced from the micron scale to the nano scale. These modifications have thus improved the versatility and the applicability of the microspheres to a variety of applications. Modifications involving nanoparticles have resulted in the first class of optical contrast agents for optical coherence tomography (OCT). Modifications with receptor specific peptides have generated microspheres that can be targeted to tumor cells. And finally, modifications of the microspheres with nucleic acids have opened the door to new applications in gene therapy. |
