Targeted Delivery of Molecular Cargo and Fluorescent Bioimaging Agents

Selective delivery of molecular cargo in complex biological systems is a major unsolved problem that impacts many fields of biomedical research and technology. In addition to the complexity of finding the correct target in a living animal, there is the challenge of transporting molecular cargo across the plasma membrane of a living cell. This thesis describes several methods to deliver molecular cargo to specific biological sites by targeting structures such as anionic phospholipids. Once class of these conjugates can enter into living cells via endocytic uptake while another can be transported directly across the plasma membrane by phospholipid transloases. While the efficacy of a therapeutic aget can be monitored by assaying a physiological response, this may be time consuming and require large quantities of resources. Fluorescence imaging provides a powerful and convenient method to monitor biological systems both in vitro and in vivo in real time. Therefore, there is a need for fluorescent dyes that are brighter, more photostable, and robust in biological systems. The dye described here, the squaraine rotaxane, shows significantly greater photostability and resistance to degradation in biological systems as compared to conventional fluorescent dyes. Also, it can be chemically modified to localize to different subcellular targets.