Calcium Phosphate Based Nanoshell for use in Biomedical Applications

There is much interest in the use of nanoparticles as targeted contrast agents, biosensors, targeted drug delivery vehicles, and as artificial oxygen carrieres. Nanoparticles of interest consist of liposomes/polymersomes, emulsions, micelles, and silica. Each of these nanoparticles have demonstrated efficacy in at least one of the mentioned areas but none can be effectively used universally. Liposomes, emulsions, and micelles suffer from stability issues in high turbulence environments, polymer based materials require organic solvents for their synthesis that are disadvantageous for biological applications, while silica based materials are not biodegradable. To expand the use of these nanoparticles for other applications requires major synthesis modifications, adding to the time required for implementation.

The objective of this research is to develop, characterize, and demonstrate the applicablility of a novel, versatile, calcium phosphate based, core-shell nanocarrier that can be used in the above applications with straightforward modifications. Calcium phosphate is rigid, biocompatible, and can be synthesized in biofriendly conditions. Initially, several novel synthetic methods will be developed and evaluated for reproducible calcium phosphate nanoshell synthesis and a reaction mechanism proposed. Nanoshells from 5-200 nm are deposited around a 30-200 nm liposome template first (CHAPTER 2) followed by deposition around a 100-350 nm soybean oil and perfluorocarbon emulsions (CHAPTER 3). The ability of the resultant nanoshells to effectively entrap hydrophilic pyranine, and hydrophobic pyrene while protecting them from quenching molecules (H2O2 and Cu2+) is verified (CHAPTER 4). The potential for use in targeted delivery applications is demonstrated by development of a covalent attachment method for an anti-FITC IgG antibody and horseradish peroxidase enzyme. The attachment efficiency and residual activity are quantified (CHAPTER 5). The ability of perfluorooctyl bromide cored calcium phosphate nanoshells to carry and deliver oxygen to the body is demonstrated through enzymatic assay methods (CHAPTER 6).

The calcium phosphate nanomaterial developd here shows strong potential to be a universal delivery system. The calcium phosphate shell provides protection, rigidity, stability, and a scaffold for the covalent attachment of proteins and other biomolecules. The ability to change the core hydrophobicity of the nanoshell allows potential entrapment of proteins, dyes, contrast agents, and pharmaceuticals.