Understanding the Functional Group-dependent Self-assembly and Cellular Entry of Cationic Conjugated Polymer Nanoparticles

Authors

Prakash Manandhar, 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

Kevin O'Shea

Second Advisor's Committee Title

Committee member

Third Advisor's Name

Bruce McCord

Third Advisor's Committee Title

Committee member

Fourth Advisor's Name

Jeffrey Joens

Fourth Advisor's Committee Title

Committee member

Fifth Advisor's Name

Juan Liuzzi

Fifth Advisor's Committee Title

Committee member

Keywords

Conjugated Polymer, Conjugated Polymer Nanoparticles, poly(p-phenyleneethynylene), poly(p-phenylenebutadiynylene), Scanning Ion Conductance Microscope, Helical Conjugated Polymer, siRNA delivery, Pore formation in cell membrane, Glycosaminoglycans, Self assembly, Cellular interaction of Conjugated polymer nanoparticles, Guanidine functionalized Conjugated Polymers

Date of Defense

3-26-2018

Abstract

Highly fluorescent conjugated polymers (CPs) are an important class of biomaterials used for various biological applications including labelling, sensing, and delivery of biological substances. Synthetic versatility and tunable emission make CPs a superior class of biomaterials. Understanding the structure-function relationship of CPs plays a vital role in designing high performing biomaterials. The cationic CPs are self-assembled to conjugated polymer nanoparticles (CPNs) in an aqueous environment due to their amphiphilicity. The physical and biophysical properties of CPNs are highly dependent on the chemical functionality and backbone structure of CPs. Modulation of the surface property and backbone structure of CPNs play an important role for efficient internalization of CPNs into cells. The goal of this dissertation is to understand the structure function relationship of CPNs in an aqueous environment and the change in their photo physical properties upon the self-assembly of CPNs with different backbone structure upon complexation with biologically significant polysaccharides and cell membrane.

This work presents the self-assembly of a set of four cationic CPs with different connectivity and backbone structure upon complexation with a linear polyanion hyaluronic acid (HA). The study of photo physical properties changes upon the complexation with series of Glycosaminoglycans (GAGs) provides more insight about how the self-assembly behavior of cationic CPs changes upon the exposure to negatively charged polysaccharides. The understanding of the self-assembly of CPNs with negatively charged biologically important macromolecules under in vitro conditions can give us an idea of photophysical property changes of CPNs during the treatment of CPNs in the cellular environment. The study of the interaction of CPNs with cell membranes using scanning ion conductance microscopy (SICM)-based topography, potential mapping, and confocal microscopy imaging is presented. CPNs are able to induce transient pore like feature formation on the cell membrane during the cellular internalization process. A comparative study of cellular labelling and delivery of siRNA of five CPNs with guanidine motif is presented. The subcellular localization and delivery of siRNA were dependent on the side chain hydrophilicity. The CPNs fabricated with hydrophilic aminoethoxyethanol possesses excellent cellular imaging with higher siRNA delivery.

Identifier

FIDC004087

Recommended Citation

Manandhar, Prakash, "Understanding the Functional Group-dependent Self-assembly and Cellular Entry of Cationic Conjugated Polymer Nanoparticles" (2018). FIU Electronic Theses and Dissertations. 3673.
https://digitalcommons.fiu.edu/etd/3673