Off-campus UMass Amherst users: To download campus access dissertations, please use the following link to log into our proxy server with your UMass Amherst user name and password.

Non-UMass Amherst users: Please talk to your librarian about requesting this dissertation through interlibrary loan.

Dissertations that have an embargo placed on them will not be available to anyone until the embargo expires.

Author ORCID Identifier

https://orcid.org/0000-0002-6633-7824

Document Type

Campus-Only Access for Five (5) Years

Degree Name

Doctor of Philosophy (PhD)

Degree Program

Chemistry

Year Degree Awarded

2020

Month Degree Awarded

February

First Advisor

S. Thayumanavan

Subject Categories

Biomaterials | Biotechnology | Cell Biology | Materials Chemistry | Organic Chemistry | Polymer Chemistry

Abstract

Therapeutic delivery refers to the transportation of a pharmaceutical compound to the desired target to achieve its therapeutic effect. Cationic materials are commonly employed to facilitate therapeutic delivery by interacting with cell membrane via electrostatic interaction. However, positive surface charge in cationic materials interferes the integrity of cell membrane, therefore inducing toxicity in therapeutic delivery systems at high dosage. Non-cationic materials exhibit reduced toxicity profiles comparing to cationic materials. In this dissertation, synthetic polymers are utilized to formulate non-cationic systems to expand their applications in therapeutic delivery, specifically for drug encapsulation, RNA delivery and subcellular localization. In terms of drug encapsulation, non-cationic copolymers demonstrate tunable drug loading capacities with a simple combinatorial formulation of copolymers. For RNA delivery, non-cationic RNA-polymer complexes are successfully used for the delivery of double-stranded RNA with negligible cytotoxicity, initiating the intracellular RNA interference process for gene specific regulation. Regarding subcellular localization, an end group labeling strategy for synthetic polymers is presented as a precisely controlled platform for the functionalization of polymers. With the conjugation of delocalized lipophilic cations (DLCs, commonly used mitochondrial targeting moieties), anionic polymers exhibit significantly promoted mitochondrial targeting effect than their cationic and charge-neutral analog. Meanwhile, the labeling strategy is broadly applicable for polymers with different surface charge. Fluorescently labelled polymers using such strategy are finally used to probe the effect of surface charge on the endocytic process of synthetic polymers.

DOI

https://doi.org/10.7275/acvc-cd11

Creative Commons License

Creative Commons Attribution-Noncommercial 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License

Share

COinS