Intellectual merit The goal of this project is to study the biomimetic properties of inorganic metal oxide nanoparticles in relation to their physicochemical parameters, and evaluate their antioxidant and cytotoxic effects. These studies contribute to the understanding of the mechanism of action of these particles, and of the parameters that are determining the efficacy and the therapeutic potential of these compounds. The second goal is to design robust sensing systems based on the biomimetic activity of these materials. We have found that nanoceria inactivates a variety of reactive species including superoxide, NO and peroxynitrite and have designed methods that allow real-time assessment of their activity in biological systems. As an example, experiments to evaluate the radical scavenging activity against superoxide radicals in a brain slice model indicate that cerium oxide nanoparticles is a promising therapeutic agent for the treatment of ischemic brain injury. Studies of cytotoxicity in biological models and the mechanism of action in relation with the physicochemical properties are underway. CAREER: Inorganic nanoparticles with biological properties: preparation, characterization and sensing applications Emanuela S. Andreescu, Clarkson University, DMR Addition of ceria nanoparticles inactivates superoxide released Induced superoxide production in a brain slice model of ischemia Ceria nanoparticles inactivate superoxide radicals produced in a brain slice model of ischemic damage, as quantified by a cytochrome c electrochemical biosensor. The catalytic activity for nanoceria (15 nm) was equivalent to 520 U of SOD in neutralizing superoxide for each 1  g of ceria added. The decrease in superoxide accumulation after repeated administration of ceria is likely due to the uptake and intracellular scavenging of superoxide by the nanoparticles. Real-time assessment of the superoxide anion radical scavenging activity of cerium oxide nanoparticles TEM micrographs showing the location of ceria nanoparticles within hippocampal brain slices. Ceria particles (white arrows) are located in high densities in the mitochondria and associated with neurofilaments (black arrows).

Broader Impact Integration of research into the classroom: Research based projects were implemented in the Biochemistry/Biotechnology laboratory for biomolecular science majors (34 students in Spring 2012) at Clarkson. Students were also trained in proposal writing, ethics in research and effective communication. K6-8 outreach: Developed an educational module to demonstrate the concept of biomimetic materials possessing antioxidant, radical scavenging activity. 28 students (grades 6-8) from three local schools were exposed to the topic of biomimetic materials, antioxidants, free radicals and oxidative stress. Dissemination of research and outreach to the community: 5 peer-reviewed papers published and 3 submitted with graduate and undergraduate co-authors. 1 book published. Collaboration with St Lawrence University and Dartmouth Medical School to assess the effectiveness of the materials and sensors that we develop in relevant biologically relevant environments. Dissemination of research to the local community: Potsdam Science Café, a local forum where local university professors facilitate informal public discussions of important science-related topics: Student mentoring and dissemination: 1 PhD thesis and 3 undergraduate senior thesis completed in Five presentations at the national fall 2012 ACS meeting. Five female undergraduate students participated in the project during the summer of PhD thesis and 2 undergraduate projects are underway. CAREER: Inorganic nanoparticles with biological properties: preparation, characterization and sensing applications Emanuela S. Andreescu, Clarkson University, DMR Graduate student Erica Sharpe discussing uses of biomimetic materials and demonstrating her nanoparticle based assay to students at Brasher Fall School on Spring 2012 and results of student evaluation.