REU Supplment: CAREER: Kinetics and Engineering of Functional Nanoscale Organic-Inorganic Hybrids

The proposed REU supplement will support an undergraduate student in the summer of 2007 to study the loading and stability of proteins and enzymes on and in mesoporous silica and organic/inorganic hybrid materials. This project is a new application that has arisen from studies of the synthesis of controlled-porosity materials as described in the PI's CAREER grant. A graduate student and a high school student working in Dr. Rankin's lab worked together to prepare uniform, amine-functional mesoporous silica microspheres (Fig. 1). These spheres were loaded with sulforhodamine-b (SRB, a pink dye) and tested for pHresponsive release. As figure 2 illustrates, SRB is retained in the particles in acidic conditions (pH 2) but upon placing the particles in a mildly alkaline environment (pH 9) the dye is released. Neutralizing the acidic solution also causes dynamic, rapid release of the dye. Now that we have seen pH-controlled adsorption, we intend to move in the direction of designing particles for controlled retention and release of proteins. There are two motivating applications for this, both related to the use of engineered silica in a biological context. The first is to develop systems for oral delivery of therapeutic proteins (insulin for example, or enzymes). This is not possible without a well-designed carrier because of rapid, acid-induced degradation in the stomach. If the pore size is expanded in our silica particles, and if polyamine functionalization is utilized, we hypothesize that we will be able to achieve the type of pHresponsive release of proteins that we show in Figure 2 for a small-molecule dye. The second application is for parenteral delivery of therapeutic proteins using silica carriers. Using silica as a carrier for these applications (for instance, intravenous delivery) is controversial. On one hand, silica is known to induce oxidative stress and chronic inflamation in the lungs, which leads to various diseases including silicosis. On the other, silicabased bioglass is considered to be a safe and effective orthopedic material that in some cases can be resorbed and eliminated as new tissues grow. We plan to begin addressing the controversial nature of silica nanoparticlebased therapies with a fundamental study of the effects on catalytic activity and stability of antioxidant enzyme loading into and onto engineered silica. These enzymes would overcome the oxidative stress hypothesized to induce silica toxicity.