Development of Shell-Crosslinked Knedel-like Nanoparticles as Intracellular Delivery Vehicles and Gene Regulation Agents

This dissertation focuses on the development of polymer-based nanomaterials, termed shell-crosslinked knedel-like: SCK) nanoparticles, as vehicles to carry specific guest molecules or guest structures into the cell. Detailed synthetic procedures for and characterization of well-defined block copolymers, as well as the nanostructures resulted from their self-assembly are reported. The nanoparticles exhibited different but controlled sizes and shapes, depending on the conditions for their preparation. To incorporate functionality into these materials, both pre- and post-particle functionalization methods, as well as their combination, were used. The nanostructures involved in this dissertation include protein transduction domain: PTD)-functionalized SCK, folate-functionalized SCK and cationic SCK: cSCK). Biological evaluation of each type of nanoparticles is described. For the PTD- and the folate-SCKs, a particle shape/size dependence on their ability to undergo cell uptake was found, although their trends were opposite. The cSCKs were designed to bear primary amines, which rendered the nanoparticles a positively charged character in solution that was utilized to condense and protect DNA. The cSCKs were shown to be highly effective in transporting DNA into the cell to allow the DNA to function. Peptide nucleic acids: PNAs) were also effectively transported into the cell by covalent conjugation to or electrostatically complexation with the cSCKs. Finally, the cSCKs were shown to be able to form hierarchical nanoscale structures with anionc, cylindrical SCKs, and transport the cylinders into the cell.

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Chemistry

Year dc:date.available

2009

Author dc:creator

• Zhang, Ke

Contributors dc:contributor

• Karen Wooley

• Chemistry
• Polymer
• Nanoscience
• Nanotechnology
• block copolymer
• crosslink
• drug delivery
• nanoparticle
• self-assembly
• transfection

Language dc:language

English (en)

DOI

https://doi.org/10.7936/K7HT2MC9

OAI identifier oai:identifier

oai:openscholarship.wustl.edu:etd-1396