I. Synthesis and Proton Conductivity Studies of Mesostructured Organosilicates and Bitriazole-Polymer Composites. II. Targeted Nanoparticles for siRNA Delivery

Citation

Alabi, Christopher Akinleye (2009) I. Synthesis and Proton Conductivity Studies of Mesostructured Organosilicates and Bitriazole-Polymer Composites. II. Targeted Nanoparticles for siRNA Delivery. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/9SNH-2A91. https://resolver.caltech.edu/CaltechETD:etd-05262009-145437

Abstract

The underlying theme of the research outlined in both parts of this report is centered on the ability to use synthetic design as a probe to investigate and answer fundamental mechanistic questions in an effort to improve the function of materials employed in energy and biological research. Specifically in the field of energy research, we have designed a new strategy aimed at improving the proton conductivity of organically modified silica-based polymer electrolyte membranes for use in direct methanol fuel cells. Our design involves the incorporation of the desired organic functional group into a siloxane-modified polymerizable surfactant that can be used in mesoporous silicate synthesis. This approach takes advantage of the silicate assembly mechanism, which places surfactants exclusively within the pores of the silicate at high loadings. The desired functional group is revealed upon selective cleavage after hydrothermal silicate synthesis. We have used this approach to synthesize organosilicates with different sized organic groups displaying high organic acid densities and have studied their proton conductivity under fully hydrated conditions. Under these conditions, structural diffusion via a percolated water network is the dominant mechanism of proton transport.

With regards to membranes for use in hydrogen fuel cells that operate best at temperatures above the dew point of water, the need for an alternative to water as the proton conducting medium is desired. Towards this end, we designed a new nitrogen-containing heterocycle (NCH), 4,4-1H-1H-bi-1,2,3-triazole (bitriazole) capable of mimicking water in the solid state and have investigated its ability to conduct protons in the presence of polyethylene oxides under anhydrous conditions. With numerous chemical tools at our disposal, we probed the mechanism of proton conduction and confirmed the bitriazole proton to be the source of anhydrous proton conductivity. Our data suggests structural diffusion as the dominant transport mechanism via synergistic interactions between bitriazole and polyethylene oxides in the polymer-rich region of the composite material that is encapsulated by a crystalline nonconductive bitriazole framework.

In the second part of this report, we shift our focus to the investigation of antibody-mediated targeting, using our well-established cyclodextrin polycation (CDP) nanoparticles containing therapeutic oligonuleotides, to epitopes expressed at the surface of cancer cells as a means of increasing site-specific therapeutic delivery. To do this, we synthesized fragments of anti-CD20 (rituximab) and conjugated them to flexible poly(ethylene glycol) (PEG) linkers with terminal adamantane groups that can interact with the cyclodextrins on the surface of the CDP nanoparticle via the formation of an inclusion complex. With the PEGylated antibody fragments in hand, we investigate, via a B-cell lymphoma model, the binding characteristics of the targeting ligands as well as their effect on the binding, internalization, and efficacy of the targeted CDP-nucleic acid therapeutic nanoparticles.

Thesis Files