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APPLICATIONS OF ELASTIN-LIKE POLYPEPTIDES IN IMAGING AND DRUG DELIVERY FOR BLADDER CANCER USING FACILE ORGANIC EXTRACTION PURIFICATION

thesis
posted on 01.01.2021, 00:33 by Craig J Sweet
The work described in this dissertation encompasses the design, production, purification, and testing of a set of novel elastin-like polypeptides (ELP). Our aim in developing these proteins was for drug delivery in Bladder Cancer (BC). BC has consistently shown the highest reoccurrence rates of nearly any cancer, thus putting a heavy burden on patient quality of life, and healthcare cost among its many other clinical challenges (Chapter 1). To reduce such a burden, we sought to produce a targeted ELP which could be used first as a contrast agent, and then provide the seminal work for a drug delivery system. Throughout the development process, a unique organic solvent-based extraction was developed for the expedited purification of ELP. Beyond being orders of magnitude faster than any previously described method, the organic extraction was able to remove key host contaminants (Chapter 2). While great success was achieved using this facile organic extraction, complete removal of organic solvents and minor contaminants became difficult and laborious to achieve. These challenges post organic solvent extraction were overcome by implementing a crucial precipitation step. The newly developed extraction-precipitation method was then tested using various ELP to show the universality of this purification method. (Chapter 3). Using our newly established method, we demonstrated the clinical value by the purification of a targeting ligand, epidermal growth factor (EGF), fused to an ELP. The performance of this construct was tested on multiple bladder cancer models, as a potential contrast agent, and was compared against non-targeted ELP (Chapter 4). A summation and forward look into applications of my work, both the novel purification scheme, and the potential impact of targeted ELP proteins in bladder cancer were explored (Chapter 5).

History

Degree Type

Doctor of Philosophy

Department

PULSe (Life Sciences)

Campus location

West Lafayette

Advisor/Supervisor/Committee Chair

Dr. David H. Thompson

Additional Committee Member 2

Dr. Andrea Kasinski

Additional Committee Member 3

Dr. Kevin Solomon

Additional Committee Member 4

Dr. Gaurav Chopra