Date of Completion

5-9-2014

Embargo Period

5-9-2014

Keywords

α-ZrP, bZrP, Nanomaterials, Cationization, Protein-o-philic, Intercalation, Biofunctionalization, Catalysis, Nanoparticles, Cellular Imaging

Major Advisor

Prof. Challa V. Kumar

Associate Advisor

Dr. Rajeswari M. Kasi

Associate Advisor

Dr. Yao Lin

Associate Advisor

Dr. Fatma Selampinar

Associate Advisor

Dr. Liisa Khun

Field of Study

Chemistry

Degree

Doctor of Philosophy

Open Access

Open Access

Abstract

This dissertation focuses on the rational design of new class of functional biomaterials using tools of nanotechnology to improve the unique functional properties of proteins. In particular, inorganic layered material, alpha-Zr(IV)phosphate (alpha-ZrP) was biofunctionalized by pre-adsorption of cationized bovine serum albumin (cBSA), which act as a sacrificial protein, to promote enzyme binding in a predictable manner. Enzyme/inorganic hybrids were further characterized using various biophysical and bioanalytical tools to evaluate the structural integrity, catalytic activity and the thermal stability of bound enzymes. Enzyme binding to biofunctionalized alpha-ZrP (bZrP) indicated exceptionally high loading and the binding is linearly proportional to the number of residues present in the enzyme or its volume, providing a powerful, new predictable tool for binding.

We also developed a simple, efficient and versatile method to synthesize inorganic nanoparticles, as opposed to nanoplates described above, of well-defined shapes, controlled size and defined surface functionalities. Nanoparticles of a wide variety of materials such as proteins, nucleic acids,small organic molecules, metal complexes, inorganic solids and organic polymers were prepared by controlled precipitation in a microscopic reactor, which was rapid and highly reproducible.

The above studies were extended to synthesize highly stable, strongly fluorescent, protein-based nanoparticles (Prodots), which are urgently needed for nanomedicinal applications. Prodots in the size range of 15-50 nm were prepared and they have been rapidly uptaken by human oral cancer cells. Thus, they could serve as potential carriers for small molecules or for the transport of biologically active proteins into cells, as alternatives to DNA transfection studies.

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