Grant: Operating Grant

Nanotechnologies have been widely implemented for a variety of applications from cosmetics, apparel, and computers to life sciences and medicine, the latter of which is referred to more specifically as nanomedicines. Nanoparticles (NPs) made of different materials are beginning to fulfill some needs in "nano" and regenerative medicine, i.e. to provide more sensitive means of early detection and measurements of pathological changes in the sick tissues, and to promote tissue repair. However, the effects of these nano-sized biotechnological products on brain cells are unknown. We have been investigating different NPs for the purpose of sensing, imaging and delivering drugs. Gold and some other metallic nanoparticles remarkably affected resident immune cells of the brain, known as microglia. Microglia are the "sensors" of the brain and they can either protect or adversely affect the neurons. The most interesting discovery from our studies is that we can regulate the degree and duration of microglial activation by carefully designing NPs. We also found that nanoparticles can modulate microglial cell functions. This proposal investigates how nanoparticles alter microglial cell activity and how multifunctional systems can be used to repair and restore healthy microglial and neuronal cell functions. In the present studies, we will, (i) develop, test and optimize novel nanostructures as sensors and nano-therapeutics (so called nanomedicines), (ii) use animal models of neuroinflammation to test novel systems with novel properties to normalize excessively activated microglia and help them to restore normal functions, (iii) investigate molecular mechanisms underlying the impairments and therapeutic interventions to enhance their effectiveness. These studies will advance our understanding of the molecular basis of NP action and demonstrate the potential of nano-based systems as safe and effective therapeutics to promote repair and recovery in the compromised nervous system.