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Author ORCID Identifier
N/A
AccessType
Open Access Dissertation
Document Type
dissertation
Degree Name
Doctor of Philosophy (PhD)
Degree Program
Polymer Science and Engineering
Year Degree Awarded
2018
Month Degree Awarded
May
First Advisor
Gregory N. Tew
Subject Categories
Biological Engineering | Biomaterials | Immunoprophylaxis and Therapy | Polymer Chemistry
Abstract
The plasma membrane is a major obstacle in the development and use of biomacromolecules for intracellular applications. Consequently, proteins with intracellular targets represent an enormous, yet under studied avenue for therapeutics. Extended research has aimed at facilitating intracellular delivery of exogenous proteins using protein transduction domains (PTDs), which allow transport of bioactive molecules into cells. Synthetic polymers, inspired by PTDs, provide a well-controlled platform to vary molecular architecture for structure activity relationship studies. Specifically, this thesis focuses on the use of ring-opening metathesis, a facile and efficient polymerization technique, through which we can vary structural parameters to optimize delivery of non-covalently encapsulated proteins. The aim was to characterize, optimize, and utilize PTD mimics (PTDMs) for functional protein delivery. Fluorescently labeled cargo were used to elucidate the predominant cellular entry mechanism for the PTDMs and were compared to their ability to deliver protein into cells. A series of polymers was designed around the most membrane active polymers to explore the incorporation of guanidine and hydrophobic moieties, yielding a PTDM capable of high protein delivery into a variety of cell types. The PTDM was then explored for use as a vaccine delivery reagent into immune cells. The ability to have a specific response with the cargo of interest verifies cytosolic delivery using the PTDMs and provides valuable insight into their use to affect intracellular pathways.
DOI
https://doi.org/10.7275/pmkg-tj22
Recommended Citation
Backlund, Coralie, "Polymeric Peptide Mimics for Protein Delivery" (2018). Doctoral Dissertations. 1216.
https://doi.org/10.7275/pmkg-tj22
https://scholarworks.umass.edu/dissertations_2/1216
Included in
Biological Engineering Commons, Biomaterials Commons, Immunoprophylaxis and Therapy Commons, Polymer Chemistry Commons