(5cl) Neural Nanotechnology: Nanomaterials for Molecular Imaging and Therapy

The potential of nanotechnology in biology and medicine has been sufficiently demonstrated on a general level by a number of proof-of-principle studies. My proposed research program seeks to apply nanotechnology in tackling significant problems in neural systems. With this overall goal in mind, I will pursue the following specific thematic areas: (1) Probing neuron cell biology by nanotechnology. The optical properties of quantum dots will be used to probe the transport phenomena in neurons; the electric properties of quantum dots will be used to interface with neurons; the mechanical properties of iron oxide nanocrystals will be used to apply force on neurons. (2) Treating neural diseases by nanotechnology. Insights into the workings of neural systems obtained from fundamental research will be applied to develop newer treatment strategies. For example, quantum dots will be used to examine how nanoparticles improve drug delivery across the blood brain barrier. Further, multifunctional nanoparticles will be used for combined imaging and therapy. (3) Platform nanotechnology. Efforts will be made to optimize the surface coating of nanoparticles for decreased non-specific binding and improved biocompatibility, to reduce the size of nanoparticles for minimized interference with the biological events, and to decrease the fluorescence intermittency of quantum dots for non-stopped tracking of biomolecular transport. Combined with newer delivery, targeting, imaging and magnetic manipulation techniques, these nanoparticles are expected to ultimately achieve single molecule-level probing at regular basis in live cells.

My previous research forms the foundation for the above-proposed work, for example: (1) Engineering nanomaterials. I have created drug delivery devices based on combinations of polymer-based and lipid-based systems. I have assembled composites of semiconductor quantum dots and iron oxide nanoparticles. (2) Molecular imaging. I have used quantum dots to image Tat peptides in live cells, especially the downstream events of cellular uptake of Tat-quantum dots. I have been the first to obtain the image of single QDs in live cell cytoplasm. I have successfully used QDs to track motor proteins in live cells. (3) Transport phenomena in biological systems. Experimentally, I have made discoveries in the intracellular trafficking and cellular secretion of Tat-quantum dots, as well as the dynamics of motor proteins. Theoretically, I have investigated the transport of nanoparticles in cytoplasm and the transport of drugs in drug delivery devices. The predictions of the theoretical studies have been confirmed by experimental results.