Author's School

Graduate School of Arts & Sciences

Author's Department/Program

Chemistry

Language

English (en)

Date of Award

January 2009

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Chair and Committee

Karen Wooley

Abstract

This dissertation research is primarily focused on the preparation of polymer-based nanostructures as potential diagnostic agents and therapeutics delivery vehicles. Various polymers, nanoparticles and conjugation techniques were developed to meet the specific requirements of each application. Shell crosslinked nanoparticles: SCKs) are characterized by their structural integrity and available functionality to attach multiple agents on the shell, such as receptor-recognizing or receptor-specific ligands, .imaging agents, Cell transduction components, etc. In this work, SCKs derived from amphiphilic poly(acrylic acid)-block-polystyrene: PAA-b-PS) have been studied as potential diagnostic and therapeutic agent delivery vehicles: Chapters 2 and 4). SCK nanoparticles bearing a cyclic KCRGDC peptide which specifically binds to avb3 integrin receptor were developed as potential delivery system for treatment of acute vascular injuries. Methods were developed to afford "clean" nanoparticles with significant binding abilities. Nanoscale contrast agents for magnetic resonance imaging were also developed based on SCKs derived from PAA-b-PS and a Gadolinium-DOTA complex to achieve high relaxivity contrast agents. Our results showed that SCKs may serve well as potential diagnostic and therapeutic agent delivery vehicles Meanwhile, these SCKs were also studied as the template for mineralization of silver nanoparticles, along with a nuleating peptide, AG-P35, as a co-template: Chapter 5). Various morphologies of silver nanoparticles were obtained and it's found that the morphology was highly dependent on polymer and peptide concentrations and incubation time. Micelles from a novel hyperbranched fluoropolymer with small sizes able to pass the blood brain barrier were synthesized: Chapter 3). After conjugation with F3 peptide which targets to nucleolin in most tumor cells, and loaded with doxorubicin as the drug to kill the tumor cells, both in vitro and in vivo studies were performed. It was found that F3-peptide conjugated nanoparticle not only specifically bind to the tumor-associated angiogenic endothelial cells, doxorubicin carried by these nanoparticles also caused apoptotic effects on the targeted tumor cells.

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Permanent URL: http://dx.doi.org/10.7936/K74J0C4B

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