Date of Award

8-2013

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Legacy Department

Bioengineering

Advisor

Alexis, Frank

Committee Member

Simionescu , Dan

Committee Member

Wei , Yanzhang

Committee Member

Whitehead , Dan

Abstract

The main focus of this research was to evaluate the ability of a novel multifunctional nanoparticle to mediate drug delivery and enable a non-invasive approach to measure drug release kinetics in situ for the treatment of cancer. These goals were approached by developing a nanoparticle consisting of an inorganic core (i.e. gadolinium sulfoxide doped with europium ions or carbon nanotubes). This was coated with an external amphiphilic polymer shell comprised of a biodegradable polyester (i.e. poly(lactide) or poly(glycolide)), and poly(ethylene glycol) block copolymer. In this system, the inorganic core mediates the imaging aspect, the relatively hydrophobic polyester encapsulates hydrophobic anti-cancer drugs, and poly(ethylene glycol) stabilizes the nanoparticle in an aqueous environment.
The synthesis of this nanoparticle drug delivery system utilized a simple one-pot room temperature ring-opening polymerization that neglected the use of potentially toxic catalysts and reduced the number of washing steps. This functionalization approach could be applied across a number of inorganic nanoparticle platforms. Coating inorganic nanoparticles with biodegradable polymer was shown to decrease in vitro and in vivo toxicity. Nanoparticles could be further coated with multiple polymer layers to better control drug release characteristics. Finally, loading polymer coated radioluminescent nanoparticles with photoactive drugs enabled a mechanism for measuring drug concentration in situ. The work presented here represents a step forward to developing theranostic nanoparticles that can improve the treatment of cancer.

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