Conjugated Polymer-Based Biomaterials Through Controlled Self-Assembly

Authors

Megan Twomey, Florida International UniversityFollow

Document Type

Dissertation

Degree

Doctor of Philosophy (PhD)

Major/Program

Chemistry

First Advisor's Name

Joong Ho Moon

First Advisor's Committee Title

Committee Chair

Second Advisor's Name

Konstantinos Kavallieratos

Second Advisor's Committee Title

Committee Member

Third Advisor's Name

Watson Lees

Third Advisor's Committee Title

Committee Member

Fourth Advisor's Name

Anthony McGoron

Fourth Advisor's Committee Title

Committee Member

Fifth Advisor's Name

Kevin O’Shea

Fifth Advisor's Committee Title

Committee Member

Keywords

Conjugated polymers, self-assembly, fluorescent, cancer cell

Date of Defense

3-9-2016

Abstract

Synthetic polymeric materials have gained significant use as biological materials (biomaterials) in biomedical and pharmaceutical applications. As a result, a demand for well-defined polymers with tunable properties has emerged. The synthetic versatility of polymeric biomaterials allows the opportunity to understand the structure-property relationship of materials and their cellular interactions. A novel class of polymeric biomaterials are conjugated polymers (CPs), which possess desirable physicochemical and excellent photophysical properties, including inherent fluorescence. The synthetic versatility of CPs allows easy modification of the conjugated backbone to tune emission and side chain structures to adjust biocompatibility through increased water solubility, controlled biodegradability, and incorporation of targeting units. The aim of this dissertation is to better understand conjugated polymer nanoparticle (CPN) structure and self-assembly in an aqueous environment, and how those structural features affect cellular interactions to establish a structure-function relationship.

This work presents the fabrication of several different CPNs for cancer cell targeting and labelling, and differentiation of biologically important molecules. Core−shell nanoparticles were prepared using a semi-flexible cationic CPN complexed with hyaluronic acid (HA), a polyanion. The resulting CPNs exhibited high cancer cell specificity with low adsorption to normal cells, as a result of HA’s affinity towards overexpressed receptors on cancer cell surface. A systematic investigation on the aggregation properties of CPNs that vary by side chain and backbone structures in response to different biologically important anionic polysaccharides in a complex biological medium was conducted. Mitochondria-specific CPNs were fabricated from a semi-flexible CPN modified with the mitochondrial-targeting triphenylphosphonium (TPP) group. The subcellular localization and cellular toxicity were dependent on backbone flexibility, hydrophilicity, and molecular weight. Dual-targeting CPNs grafted with folic acid (FA) side chains and complexed with hyaluronic acid (HA) were fabricated for improved uptake and bioimaging of cancer cells.

The work presented here shows how modifications to CPN backbone and side chain structures modulate their cellular interactions. The physicochemical and biophysical properties of CPNs affect biocompatibility and understanding those properties will lead to the development of novel CP-based biomaterials.

Identifier

FIDC000272

Recommended Citation

Twomey, Megan, "Conjugated Polymer-Based Biomaterials Through Controlled Self-Assembly" (2016). FIU Electronic Theses and Dissertations. 2452.
https://digitalcommons.fiu.edu/etd/2452