Doctor of Philosophy, University of Akron, 2019, Chemical Engineering

In the study of this Ph.D. dissertation, two research topics related to zwitterionic materials have been investigated. Even though the applications have different objectives, the unique properties that existed in zwitterionic materials have, including charge property and antifouling property, have been used in both of research. The first topic is the development of zwitterionic-peptides gene delivery system. The gene delivery system, with high efficacy, low toxicity, long blood circulation time and targeting the specific cancer cell, is investigated. The second topic is the functionalization of protein therapeutics with zwitterionic polymers. The protein therapeutics with better solubility, stability, and activity is developed. The non-viral gene delivery system is under research due to their low toxicity, low immunogenic and large DNA loading size in gene therapy. Peptides gene delivery system is reported with the cationic charge and buffering effect which overcomes the barrier and delivery DNA into the nucleus. In our group, the economic dextran-peptide hybrid gene delivery system was developed with high transfection efficiency and low toxicity. The first topic of my research was expanded as a continuous work under the same research interest. The effect of the design of peptides length, zwitterionic group and targeting group was studied for the optimization objects on achieving low toxicity, transfection efficiency and blood circulation time, which was summarized into three research projects under this topic. The system was adjusted by the peptides length for toxicity and economic purpose. The system was functionalized with the zwitterionic group for improved stability, enhanced endosomal escape and longer blood circulation time. The system was also conjugating with targeting ligand for targeting gene delivery. It was found that the shorter length of peptides will not provide enough charge to form stable micelle with report DNA. The zwitterionic functionalized (open full item for complete abstract)

Committee: Gang Cheng (Advisor); Jie Zheng (Advisor); George Chase (Committee Member); Lingyun Liu (Committee Member); Ge Zhang (Committee Member); Coleen Pugh (Committee Member) Subjects: Biomedical Engineering; Chemical Engineering; Polymers

Master of Science, Miami University, 2020, Chemistry and Biochemistry

This thesis describes changes in structure and activity of lactate dehydrogenase in solution containing the Pluronic F127 polymer. The LDH structural study in Pluronic solutions is carried out by fluorescence and circular dichroism spectroscopy, and compared to that with polyethylene glycol. The LDH structure is more stabilized by the Pluronic F127 polymer than PEG against 20% acetonitrile in the aqueous solution. The change in LDH activity with Pluronic F127 is studied by flow injection analysis in conjunction with fluorescence. The LDH will denature and significantly lose its activity under room temperature over time. The presence of 5% Pluronic F127 in the solution will stabilize LDH for at least 96 hours with only a 3-8% loss in activity, comparable to polyethylene glycol. This thesis also provides a study of electrophoresis of low molar mass peptides (< 2 kDa) using the Pluronic F127 gel as the supporting medium, followed by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) detection. Pluronic polymers suppress MALDI-MS signals of peptides but can be removed using ultrafiltration with a 10 kDa membrane filter. Separation of a four-peptide mixture pre-stained by Remazol Brilliant Blue was unsatisfactory. Further gel modifications should be carried out for electrophoresis separation of peptides.

Committee: Neil Danielson (Advisor); Hang Ren (Committee Chair); Benjamin Gung (Committee Member); Ann Hagerman (Committee Member) Subjects: Chemistry