(4a) Surface Functionalization of Nanomaterials to Elicit "Smart" Properties

Rapid advances in the field of nanotechnology have brought enormous potential for improving the quality of life. The effects of this growth are now being felt in such varied industries as drug delivery, catalysis, tissue engineering, renewable energy, and optical coatings, to name just a few. While the control of length scales at the nanometer level alone yields some exciting properties, further functionalization of the surface with ?smart? ligands that provide environment-responsive performance is generating tremendous interest. My research goals are towards the development of novel, response nanomaterials for a broad field of applications. During this poster session, I will present some of the work done in developing functional nanoparticles and nanocomposites for applications in biocatalysis and drug delivery, and discuss the future potential of this technology.

My graduate research was focused on the development of a nanoporous organic-inorganic composite matrix, using sol-gel techniques, for enzyme immobilization. With proper management of surface energies, we developed an organic-inorganic hybrid material with the following desirable properties: 1) high surface area (~650 m2/g) and uniform surface functionalization which together yielded an extremely high loading capacity (>700 mg protein/g matrix); 2) complete retention of enzyme's catalytic efficiency; 3) good pH and thermal stability; and 4) open pore morphology to facilitate substrate/production transport. The extremely high enzymatic activity of this material allowed for reactor miniaturization, which was validated with large-scale, GLP production of a therapeutic peptide (currently undergoing preclinical evaluation for Investigational New Drug approval under a $2.4 million NIH SBIR Phase II Continuation grant).

This material technology was further enhanced during my postdoctoral research with the inclusion of microenvironment-responsive biopolymers within the inorganic matrix for drug delivery applications. Particles formed with this nanocomposite displayed pH-dependent mucoadhesive and swelling properties ? allowing for targeted and controlled delivery of drugs to the oral cavity, stomach, or intestinal tract. We have specifically pursued the utilization of this material for oral delivery of insulin and antibiotics. Additionally it was found that this nanocomposite could be utilized to modulate water activity close to the surface, which in turn would provide control of immobilized enzyme activity ? yielding control of both reaction extent and side-product generation. There is also potential for this material in wound healing and tissue engineering, as well as in separation processes. I also served as group leader for the MION sub-group, of Dr. Victor Yang's lab (Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor MI), which focused on the utilization of magnetic nanoparticles for simultaneous imaging and therapy of brain tumors. In this capacity, I mentored and trained an undergraduate student, five PhD students, and four postdoctoral fellows, a group which has already produced 10 peer-reviewed papers with more in preparation.

Overall, I have an extensive background, and had success, in the development of novel nanomaterials ? both functional nanoparticles and nanocomposites (yielding 4 patent applications). I have displayed leadership abilities by maximize the productivity of a diverse group of students/researchers. Additionally, I am very familiar with the grant funding mechanism - having served as ad hoc member for six different NIH SBIR grant review committees, and successfully obtained more than $3 million in NIH grant funding for the various projects. The common thread I have going through all my research interests is the surface modification of nanomaterials to elicit "smart" properties. I expect to initially continue the development of novel, environment-responsive nanoparticles for cancer therapy and nanocomposite materials for oral drug delivery, while I evaluate the other applications for this technology.