Date of Award

2016

Degree Type

Dissertation

Degree Name

Doctor of Engineering

Department

Washkewicz College of Engineering

First Advisor

Holland, Nolan

Subject Headings

Biomedical Engineering, Biomedical Research, Nanoscience, Nanotechnology

Abstract

Theranostics is a promising field that aims to combine therapeutics and diagnostics into single multifunctional formulations. This field is driven by advancements in nanotechnology and specifically in the creation of multifunctional nanoparticles capable of providing the necessary functionalities. Elastin-like polypeptides (ELPs) are a class of environmentally responsive biopolymers that are known to undergo a transition in response to various stimuli. The organic nature of ELPs along with the ability to control their design at the gene level and the aforementioned responsive behavior make them a promising candidate for use in theranostic systems. The system presented here is one of the first examples of using ELPs as the base for multifunctional theranostic nanoparticles. Presented in this study is a fully protein based self-assembling nanoparticle system based on micelles of ELPs for use in theranostic applications. Micelle forming ELP constructs have been modified through the fusion of the protein based MRI contrast agent CA1.CD2 to the C terminal of existing protein constructs. Micelles were then crosslinked into stable nanoparticles that relied only on changes in temperature to drive the transition. In addition to that, a targeting peptide has been added to the system as well to provide active targeting to cancer cells. As a contrast agent the system has been shown to bind and retain gadolinium while effectively providing contrast in T1 weighted imaging and having higher relaxivity values than clinical contrast agents. Modification of the architecture of the construct through changes of the tail length, and through creation of mixtures did not drastically affect the behavior of the system demonstrating its flexibility. Here I detail, the design, synthesis of the expression, purification and characterization of all the required properties of the constructs.

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