Zwitteration: A Different Approach to Non Stick Surfaces

• Other Authors: Estephan, Zaki Georges (authoraut)
• Format: Others
• Language: English; English
• Published: Florida State University
• Subjects: Chemistry; Biochemistry
• Online Access: http://purl.flvc.org/fsu/fd/FSU_migr_etd-5611

Limiting undesired interactions of proteins with surfaces is a vital task for implementation of many technologies that require direct exposure to protein media. This includes sensors, single molecule spectroscopy studies, and nanoparticles that would act as vehicles for therapeutic agents or diagnostic agents. Current technology relies on the resistive properties of poly(ethylene glycol), PEG, to protein adsorption. PEG has been therefore the subject of thorough studies to decipher the mechanism involved in protein resistivity. The latter has been mainly attributed either to chain mobility, that would suffer from entropic penalty upon protein adsorption, or due to a hydration layer that prevents close encounter of proteins to the surface. Regardless of the mechanism, PEG has been reported to suffer from performance degradation in biological media due to oxidation, and its properties have been reported to differ with temperature. Given their biocompatibility, zwitterions have been proposed as a viable alternative mimicking the cell membrane. Polymeric zwitterions, the most commonly studied alternatives, result in an increase in the hydrodynamic size of particles upon grafting to surfaces. Control over size is essential as it controls the distribution of particles in the body. This work attempts to provide a different approach to nanoparticle stabilization against different aggregating factors to alleviate some of the above mentioned shortcomings of PEG and other polymers. A monomeric zwitterion siloxane was synthesized. The zwitterion siloxane covalently bonds to the oxide surface of nanoparticles without significantly changing their hydrodynamic size. The "zwitterated" particles remain stable even when challenged with high salt solutions or incubated with serum; two factors that are known to induce aggregation. The efficacy of the zwitterionic coating was compared head-to-head with a PEG coating for its ability to prevent protein adsorption to silica nanoparticles. The same siloxane coupling chemistry is employed to yield surfaces with similar coverages of both types of ligand on two geometrically different surfaces (nanoparticlesversusplanar). While both types of surface modification are highly effective in preventing protein adsorption and nanoparticle aggregation, the zwitterion provided monolayer-type coverage with minimal thickness whereas the PEG appeared to yield a more three-dimensional coating. A mechanism is proposed to explain the resistive properties of passivating ligands such as PEG and other neutral surfaces. The role of the passivating ligand is broken down to ion-coupled and ion-decoupled processes. The ion-decoupled process minimizes intermolecular interactions, whereas the ion-coupled mechanism prevents ion pairing between protein and surface charges which releases counterions and water molecules, an entropic driving force enough to overcome a disfavored enthalpy of adsorption. Finally, the synthesis of zwitterated iron oxide nanoparticles by co-precipitation of iron salts in presence of zwitterion siloxane as the stabilizing ligand is reported. This procedure yields superparamagnetic maghemite nanoparticles whose polydispersity varies as a function of the amount of zwitterion siloxane present during synthesis. The latter has the effect of changing the effective hydrodynamic radius of the particles from 5.4 nm to 35 nm. The presence of zwitterions on the surface is validated with thermogravimetric analysis and Diffuse Reflectance Infrared Fourier Transform. Magnetization versus applied field data shows the absence of coercive field and low magnetization values attributed to the decreasing particle size as well as the diamagnetic coating. The particles are tested for their possible use as MRI contrast agents. The calculated relaxation rates are low indicating that a high concentration of iron is needed for good contrast. Introduction of amine functionality for incorporation of targeting agents is achieved by the addition of aminopropyltriethoxysilane post-synthesis. The presence of the latter is verified by fluorescence spectroscopy. === A Dissertation submitted to the Department of Chemistry and Biochemistry in partial fulfillment of the requirements for the degree of Doctor of Philosophy. === Spring Semester, 2012. === December 15, 2011. === Biocompatible, Magnetic nanoparticles, PEG, Protein adsorption, Silica nanoparticles, Zwitterions === Includes bibliographical references. === Joseph B. Schlenoff, Professor Directing Dissertation; Teng Ma, University Representative; Michael Roper, Committee Member; Geoffrey Strouse, Committee Member; Subramanian Ramakrishnan, Committee Member.