Targeted Delivery of Molecular Cargo and Fluorescent Bioimaging Agents

Targeted Delivery of Molecular Cargo and Fluorescent Bioimaging Agents

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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. One class of these conjugates can enter into living cells via endocytic uptake. Another type can be transported directly across the plasma membrane by phospholipid translocases, providing an alternative delivery route to endocytosis. While the efficacy of a therapeutic agent must eventually 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 new 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.25 Figure 2.12: Effects of various endocytosis inhibitors on the uptake of (Tyr- ZnDPA)8-Fl into CHO cells. ... with FITC-streptavidin.. 31 Figure 3.1: Schematic diagram denoting structure activity relationship for PS transport conjugate scaffold.

Title:Targeted Delivery of Molecular Cargo and Fluorescent Bioimaging Agents
Author: James R. Johnson
Publisher:ProQuest - 2008

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