Design, synthesis, and evaluation of molecular transporters for probe, drug, and siRNA delivery

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Abstract/Contents

Abstract
My graduate studies have focused on the design, synthesis, and biological evaluation of novel probe and drug delivery technologies. This research has explored the development of new molecular transporter scaffolds with a focus on step economy and translational costs as well as evaluation of their uptake and delivery properties in cells and animals. Chapter 1 provides a historical context and overview of guanidinium-rich molecular transporter technology. Chapter 2 describes the development of a new family of guanidinium-rich oligocarbonate molecular transporter which are flexibly and efficiently assembled by a one-step oligomerization strategy. These novel oligocarbonate transporters were shown to exhibit excellent uptake properties both in cells and animal models. Chapter 3 is directed at the utility of an oligomerization approach to generate molecular transporters by the design, synthesis, and evaluation of new aphipathic co-oligomers for the delivery of siRNA, an oligonucleotide cargo of intense therapeutic interest. Amphipathic carbonate co-oligomers were prepared by an oligomerization strategy and demonstrated to effectively package, deliver, and release functional siRNA in cells. Chapter 4 describes the effects of a branched guanidinium array on the transport and delivery efficiency of releasable dendrimeric guanidinium-rich transporters. These transporters were synthesized and demonstrated to deliver and release a small molecule for turnover by its intracellular target enzyme by bioluminescence assays in cells and transgenic animal models. Chapter 5 describes the design, synthesis, and preliminary biological evaluation of lipidated molecular transporter derivatives of the immunosuppressant drug rapamycin for topical delivery.

Description

Type of resource text
Form electronic; electronic resource; remote
Extent 1 online resource.
Publication date 2011
Issuance monographic
Language English

Creators/Contributors

Associated with Cooley, Christina Barnes
Associated with Stanford University, Department of Chemistry
Primary advisor Wender, Paul A
Thesis advisor Wender, Paul A
Thesis advisor Du Bois, Justin
Thesis advisor Kool, Eric T
Advisor Du Bois, Justin
Advisor Kool, Eric T

Subjects

Genre Theses

Bibliographic information

Statement of responsibility Christina Barnes Cooley.
Note Submitted to the Department of Chemistry.
Thesis Thesis (Ph.D.)--Stanford University, 2011.
Location electronic resource

Access conditions

Copyright
© 2011 by Christina Barnes Cooley
License
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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